Dosage forms of oral drugs for release in the colon and methods of use and manufacture thereof.

Description

Dosage forms of oral drugs for release in the colon and methods of use and manufacture thereof. TECHNICAL FIELD

[0001] The present invention, in some aspects, relates to oral drug dosage forms configured to release a drug at a desired location in the colon of an individual. In other aspects, the present invention relates to methods for designing, methods for manufacturing, such as the use of three-dimensional printing, and treatment methods associated with the oral drug dosage forms described in this document. FUNDAMENTALS

[0002] Oral administration of pharmaceutical agents provides numerous conveniences to the patient, including limiting visits to the physician and avoiding more invasive drug delivery approaches such as injection or rectal administration. The colon can be a treatment site and / or a drug delivery site; however, the colon's location near the end of the gastrointestinal tract makes effective oral administration for release in the colon difficult. For example, an ingested oral drug dosage form must withstand the adverse pH conditions in the stomach, as well as the completely different pH conditions downstream of the stomach, and the mechanical stress applied by digestive processes before reaching the colon. The capabilities of conventional colon-targeted oral drug dosage forms vary in specificity and achieved release profiles.For example, some conventional colon-targeted oral drug dosage forms continuously release the drug throughout the gastrointestinal tract before the oral drug dosage form reaches the colon. This results in reduced drug availability in the colon, limited applicability to the active agents that can be released, and a higher likelihood of... Petition 870250088298, dated 09 / 29 / 2025, page 18 / 266 2 / 181 Systemic adverse effects due to drug release outside the target site. Therefore, there is still a need in the field for oral drug dosage forms capable of precise release in the colon. BRIEF SUMMARY

[0003] In certain aspects, an oral drug dosage form is provided in this document, configured to release a drug at a desired location in an individual's colon, the oral drug dosage form comprising: a drug component comprising an erodible material mixed with the drug; and a delay component not mixed with the drug, wherein the delay component is configured to prevent the release of the drug from the drug component until the oral drug dosage form reaches the individual's colon after administration, wherein the delay component comprises: a pH-based enteric element comprising an erodible material configured to erode at or above a predetermined pH value.

[0004] In some embodiments, the delay component further comprises an erodible delay element, and in which the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible delay element. In some embodiments, the pH-based enteric element at least partially prevents erosion of the erodible delay element, and the erodible delay element at least partially prevents erosion of the drug component.

[0005] In some embodiments, the oral drug dosage form additionally comprises a second drug. In some embodiments, the second drug is mixed with the drug component. In some embodiments, the oral drug dosage form additionally comprises a second drug component. Petition 870250088298, dated 09 / 29 / 2025, page 19 / 266 3 / 181 comprising an erodible material mixed with the second drug, wherein the delay component is configured to prevent the release of the second drug from the second drug component until the oral drug dosage form reaches the individual's colon after administration. In some embodiments, the delay component comprises a second erodible delay element, wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible delay element, the erodible delay element erodes before the second drug component, the second drug component erodes before the second erodible delay element, and the second erodible delay element erodes before the drug component.In some embodiments, the pH-based enteric element at least partially prevents erosion of the erodible retarding element, the erodible retarding element at least partially prevents erosion of the second drug component, the second drug component at least partially prevents erosion of the second erodible retarding element, and the second erodible retarding element at least partially prevents erosion of the drug component. In some embodiments, the erodible material of the erodible retarding element and the erodible material of the second erodible retarding element are the same. In some embodiments, the erodible material of the erodible retarding element and the erodible material of the second erodible retarding element are different.

[0006] In some embodiments, the oral drug dosage form additionally comprises a bacterial degradation portion. In some embodiments, the bacterial degradation portion is mixed with the erodible material of the erodible retardant element. In some embodiments, the bacterial degradation portion is mixed with the drug component. In some embodiments, the component Petition 870250088298, dated 09 / 29 / 2025, page 20 / 266 4 / 181 of the delay further comprises a bacterial degradation element comprising an erodible material mixed with the bacterial degradation portion, wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible delay element, the erodible delay element erodes before the bacterial degradation element, and the bacterial degradation element erodes before the drug component. In some embodiments, the pH-based enteric element at least partially prevents erosion of the erodible delay element, the erodible delay element at least partially prevents erosion of the bacterial degradation element, and the bacterial degradation element at least partially prevents erosion of the drug component. In some embodiments, the bacterial degradation portion is digestible by one or more microorganisms present in the individual's colon.In some embodiments, the bacterial degradation portion comprises one or more saccharides. In some embodiments, the one or more saccharides comprise any one or more of sucrose, glucose, xylose, fructose, maltose, galactose, pectin, galactomannan, dextran, inulin, chitosan, carrageenan, cellulose acetate propionate (CAP), peptidoglycan, gellan, xanthan gum, lentinan, psyllium polysaccharide, corn bran arabinoxylan, alginate, hyaluronic acid, fucoidan, shellac, agar, or maltodextrin. In some embodiments, the bacterial degradation element is a layer, and wherein the layer has a thickness, based on the direction of erosion, of about 0.1 mm to 5 mm. In some embodiments, the bacterial degradation element comprises a surface area exposed to the individual's gastrointestinal fluid of approximately 10 mm2 to approximately 400 mm2. Petition 870250088298, dated 09 / 29 / 2025, page 21 / 266 5 / 181

[0007] In some embodiments, the retarding component does not comprise an erodible retarding element. In some embodiments, the erodible material of the pH-based enteric element comprises one or more of hypromellose acetate succinate, hydroxypropylmethylcellulose phthalate, cellulose acetate propionate (CAP), poly(ethyl methacrylic acid-co-acrylate), or polyvinyl acetate phthalate (PVAP). In some embodiments, hypromellose acetate succinate is HPMCAS LG / LF, HPMCAS MG / MF, or HPMCAS HG / LF. In some embodiments, hydroxypropylmethylcellulose phthalate is HPMCP HP-50 or HPMCP HP-55. In some embodiments, poly(ethyl methacrylic acid-co-acrylate) is Eudragit L100-55 or Eudragit L100.

[0008] In some embodiments, the drug component comprises a top surface, a bottom surface, and one or more side surfaces, wherein the drug component is incorporated into the delay component such that erosion of the delay component, or an aspect thereof, exposes at least two surfaces of any one of the top surface, the bottom surface, or at least one or more of the side surfaces to the individual's gastrointestinal fluid. In some embodiments, the oral drug dosage form does not comprise a shell.

[0009] In some embodiments, the oral drug dosage form further comprises a shell not mixed with the drug, wherein the oral drug dosage form is configured such that the shell, or a part thereof, and the delay element prevent erosion of the drug component. In some embodiments, the direction of erosion of the delay component and / or the drug component is based on the configuration of the shell.

[0010] In some embodiments, the oral drug dosage form additionally comprises a protease scavenger and / or a Petition 870250088298, dated 09 / 29 / 2025, page 22 / 266 6 / 181 protease inhibitor. In some embodiments, the protease scavenger or protease inhibitor is mixed with the retarding component or a part thereof. In some embodiments, the protease scavenger or protease inhibitor is mixed with the erodible material of the erodible retarding element.

[0011] In some embodiments, the oral drug dosage form is configured to release the drug into, near, or downstream of any of the cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, or sigmoid colon. In some embodiments, at least 95% of the drug in the oral drug dosage form is released from the oral drug dosage form into the individual's colon. In some embodiments, less than 2% of the drug in the oral drug dosage form is released from the oral drug dosage form outside the individual's colon. In some embodiments, all of the drug in the oral drug dosage form is released from the oral drug dosage form into the individual's colon.

[0012] In some embodiments, the drug component and / or the delay component are in the form of one or more layers. In some embodiments, the pH-based enteric element layer comprises an upper surface and a lower surface, wherein the erodible delay element layer comprises an upper surface and a lower surface, wherein the drug component layer comprises an upper surface and a lower surface, wherein the lower surface of the pH-based enteric element layer is in contact with the upper surface of the erodible delay element layer, and wherein the lower surface of the erodible delay element layer is in contact with the upper surface of the drug component layer.

[0013] In some embodiments, the oral drug dosage form is configured to have more than one compartment, and in which Petition 870250088298, dated 09 / 29 / 2025, p. 23 / 266 7 / 181 minus one compartment comprises the drug component and the delay component.

[0014] In some embodiments, the pH-based enteric element erodes at or above a pH value of about 5.5. In some embodiments, the pH-based enteric element is a layer with a thickness, based on the direction of erosion, of about 0.1 mm to about 5 mm. In some embodiments, the pH-based enteric element comprises a surface area exposed to gastrointestinal fluid in the individual of about 10 mm² to about 400 mm². In some embodiments, the external surfaces of the oral drug dosage form, prior to administration to the individual, comprise the pH-based enteric element and, optionally, the shell. In some embodiments, the pH-based enteric element comprises a thermoformable material. In some embodiments, the pH-based enteric element comprises one or more of the following: stearic acid, copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, crospovidone, polyvinylpyrrolidone,Hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, hydroxypropylmethylcellulose phthalate, methylcellulose, methacrylic acid copolymer, poly(methacrylic acid-ethyl acrylate), poly(butyl methacrylate-(2-dimethylaminoethyl)-methyl methacrylate-co-methacrylate), poly(dimethylaminoethyl methacrylate-methacrylic esters), poly(ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate-co-chloride), poly(methyl acrylate-methyl methacrylate-methacrylic acid), poly(methacrylic acid-methyl methacrylate), poly(methacrylic acid-ethyl acrylate), poly(methacrylic acid-methyl methacrylate), polyethylene oxide, polyethylene glycol, polyvinyl graft copolymer caprolactam polyvinyl acetate-polyethylene glycol, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, Petition 870250088298, dated 09 / 29 / 2025, page 24 / 266 8 / 181 aminoalkyl methacrylate copolymer E, hydroxypropylmethylcellulose acetate succinate or hypromellose acetate succinate, methacrylic ester copolymer, ammonium alkyl methacrylate copolymer, ethylcellulose, polyvinyl acetate and polyvinylpyrrolidone, polyvinyl acetal diethyl aminolactate, polyvinyl acetal diethyl amino lactate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose, dextran or maltose.

[0015] In some embodiments, the pH-based enteric element erodes at or above a pH value of about 6.8. In some embodiments, the pH-based enteric element is a layer with a thickness, based on the direction of erosion, of about 0.1 mm to about 5 mm. In some embodiments, the pH-based enteric element comprises a surface area exposed to gastrointestinal fluid in the individual of about 10 mm2 to about 400 mm2. In some embodiments, the external surfaces of the oral drug dosage form, prior to administration to the individual, comprise a pH-based enteric element and, optionally, a shell. In some embodiments, the pH-based enteric element comprises a thermoformable material. In some embodiments, the pH-based enteric element comprises one or more of: poly(methacrylic acid, methyl methacrylate); poly(methacrylic acid, methyl methacrylate), methyl acrylate, methyl methacrylate and methacrylic acid.In some embodiments, the pH-based enteric element comprises one or more of the following: Eudragit L 100, Eudragit L 12.5, Eudragit L 12.5P, Eudragit L 100-55, Eudragit L 30D, Eudragit S 100, Eudragit S 12.5, Eudragit S 12.5P, Eudragit FS 30D. In some embodiments, the pH-based enteric element comprises one or more of the following: stearic acid, copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, crospovidone, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, hydroxypropylmethylcellulose phthalate, methylcellulose, methacrylic acid copolymer, poly(acid). Petition 870250088298, dated 09 / 29 / 2025, page 25 / 266 9 / 181 ethyl methacrylate-co-acrylate), poly(butyl methacrylate-co-methacrylate of (2-dimethylaminoethyl)-co-methyl methacrylate), poly(dimethylaminoethyl methacrylate-methacrylic esters), poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride), poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid), poly(methacrylic acid-co-methyl methacrylate), poly(methacrylic acid-co-ethyl acrylate), poly(methacrylic acid-co-methyl methacrylate), polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, hydroxypropylmethylcellulose acetate succinate or hypromellose acetate succinate, methacrylic ester copolymer, ammonium alkyl methacrylate copolymer, ethylcellulose,polyvinyl acetate and polyvinylpyrrolidone, polyvinyl acetal diethyl aminolactate, polyvinyl acetal diethyl amino lactate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose, dextran or maltose.

[0016] In some embodiments, the erodible delay element prevents the release of the drug component from the drug for at least about 10 minutes after the erodible delay element comes into contact with gastrointestinal fluid in the individual. In some embodiments, the erodible delay element is a layer with a thickness, based on the direction of erosion, of about 0.1 mm to 5 mm. In some embodiments, the erodible delay element comprises a surface area exposed to gastrointestinal fluid in the individual of about 10 mm2 to about 400 mm2. In some embodiments, the erodible delay element comprises a thermoformable material. In some embodiments, the erodible retarding element comprises one or more of the following: stearic acid, medium-chain triglycerides, glyceryl distearate, propylene glycol monolaurate, propylene glycol caprylate, polyoxyl-6 oleoyl glycerides, PEG-6 stearate, PEG-32 stearate, Petition 870250088298, dated 09 / 29 / 2025, p. 26 / 266 10 / 181 linoleoyl polyoxyl-6 glycerides, lauroyl polyoxyl-32 glycerides, caprylocaproyl polyoxyl-8 glycerides, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan oleate, glyceryl monolinoleate, copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, crospovidone, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, hydroxypropylmethylcellulose phthalate, methylcellulose, methacrylic acid copolymer, poly(methacrylic acid-ethyl acrylate), poly(butyl methacrylate-(2-dimethylaminoethyl)-co-methacrylate methyl), poly(dimethylaminoethyl methacrylate-methacrylic co-esters), poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride), poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid), poly(methacrylic acid-co-methyl methacrylate),poly(methacrylic acid-ethyl methacrylate), poly(methacrylic acid-methyl methacrylate), polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate E copolymer, hydroxypropylmethylcellulose acetate succinate or hypromellose acetate succinate, methacrylic ester copolymer, ammonium alkyl methacrylate copolymer, ethylcellulose, polyvinyl acetate and polyvinylpyrrolidone, polyvinyl acetal diethyl aminolactate, polyvinyl acetal diethyl amino lactate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose, dextran, maltose, lauroyl glycerides polyoxyl-32, caprylocaproyl glycerides polyoxyl-8, castor oil polyoxyl (35), vitamin E succinate polyethylene glycol, hydrogenated castor oil PEG-40,glyceryl monolinoleate or glyceryl dibehenate.

[0017] In some embodiments, the drug component is not in direct contact with the pH-based enteric element. In some Petition 870250088298, dated 09 / 29 / 2025, p. 27 / 266 11 / 181 In some embodiments, the drug component is a controlled-release drug component. In some embodiments, the drug component is a prolonged-release drug component. In some embodiments, the drug component is an immediate-release drug component. In some embodiments, the drug component is configured to release the drug from the oral drug dosage form over at least about 1 hour. In some embodiments, the drug component is configured to provide a drug release profile comprising a zero-order release profile, a first-order release profile, a delayed-release profile, a pulsed-release profile, an iterative pulsed-release profile, an immediate-release profile, or a prolonged-release profile, or a combination thereof. In some embodiments, the drug release is based, at least partially, on an in vitro dissolution study.In some embodiments, drug release is based, at least partially, on an in vivo dissolution study. In some embodiments, the drug component has a drug mass portion (mp) of about 0.05 to about 0.6. In some embodiments, the weight ratio between the drug component and the retardant component is about 1:10 to about 10:1. In some embodiments, the drug component is a layer with a thickness, based on the direction of erosion, of about 0.1 mm to about 5 mm. In some embodiments, the drug component comprises a surface area exposed to gastrointestinal fluid in the individual of about 10 mm² to about 400 mm². In some embodiments, the drug component comprises a thermoformable material. In some embodiments, the drug component comprises one or more of the following: copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer. Petition 870250088298, dated 09 / 29 / 2025, page 28 / 266 12 / 181 nilacetate, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, hydroxypropylmethylcellulose acetate succinate, hypromellose acetate succinate, hydroxypropylmethylcellulose phthalate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose or dextran 70. In some embodiments, the oral drug dosage form additionally comprises one to four additional drug components.

[0018] In some embodiments, the drug is an anti-inflammatory agent, nonsteroidal anti-inflammatory agent, steroid, immunosuppressant, antibiotic, biological agent, antineoplastic agent, analgesic, anesthetic, anticonvulsant, antidiabetic agent, antihistamine, anti-infective, antineoplastic, antiparkinsonian agent, antirheumatic agent, appetite stimulant, appetite suppressant, blood modifier, bone metabolism modifier, cardiovascular agent, central nervous system depressant, central nervous system stimulant, decongestant, dopamine receptor agonist, electrolyte, gastrointestinal agent, immunomodulator, muscle relaxant, narcotic, parasympathomimetic, sympathomimetic, sedative, hypnotic, or vaccine. In some embodiments, the anti-inflammatory agent is a JAK inhibitor. In some embodiments, the JAK inhibitor is tofacitinib or a pharmaceutically acceptable salt thereof.In some modalities, the anti-inflammatory agent is mesalazine, sulfasalazine, or balsalazide. In some modalities, the nonsteroidal anti-inflammatory agent is ibuprofen or diclofenac. In some modalities, the steroid is prednisolone, budesonide, or fluticasone. In some modalities, the immunosuppressant is azathioprine, cyclosporine, or methotrexate. Petition 870250088298, dated 09 / 29 / 2025, page 29 / 266 13 / 181 In some embodiments, the biological agent is a peptide, a protein, an antibody or a fragment thereof, or a nucleic acid. In some embodiments, the antibody is infliximab, adalimumab, certolizumab pegol, golimumab, or ustekinumab. In some embodiments, the antineoplastic agent is fluorouracil, methotrexate, dactinomycin, bleomycin, etoposide, taxol, vincristine, doxorubicin, cisplatin, daunorubicin, etoposide, raltitrexed, or oxaliplatin, or a combination thereof. In some embodiments, the oral drug dosage form comprises approximately 0.01 mg to approximately 500 mg of the drug.

[0019] In some embodiments, the oral drug dosage form additionally comprises an excipient. In some embodiments, the excipient comprises one or more of an absorption enhancer, a pH-reducing agent, or a disintegrant. In some embodiments, the excipient is mixed with the drug component.

[0020] In some embodiments, the shell comprises an insulating material impermeable to body fluids. In some embodiments, the insulating material comprises one or more of ethylcellulose (EC), dibutyl sebacate (DBS), and titanium dioxide. In some embodiments, the insulating material is a non-erodible material. In some embodiments, the insulating material is an erodible material with a pH-based erosion and / or erosion rate that allows complete release of the drug from the oral drug dosage form before exposure of the drug component to body fluids due to shell erosion.

[0021] In another aspect, a commercial batch of any oral drug dosage form described herein is provided in this document, wherein the commercial batch has a standard deviation of about 0.05 or less for each of the following: a quantity of a drug in the oral drug dosage form; a weight of the oral drug dosage form; a maximum transverse dimension of the form Petition 870250088298, dated 09 / 29 / 2025, p. 30 / 266 14 / 181 of oral drug dosage forms; and a cross-sectional dimension perpendicular to the maximum cross-sectional dimension of the oral drug dosage form. In some embodiments, the commercial batch comprises at least approximately 1000 of the oral drug dosage forms.

[0022] In another aspect, a method for three-dimensional (3D) printing of any oral drug dosage form described herein is provided in this document, the method comprising dispensing materials according to a layer-by-layer model of the oral drug dosage form to print the oral drug dosage form, wherein each layer of the layer-by-layer model is printed by dispensing, as required, a layer of: (a) a shell material to form any part of a shell in the layer; (b) a drug component material to form any part of a drug component in the layer; (c) a pH-based enteric element material to form any part of a pH-based enteric element in the layer; (d) an erodible retardant element material to form any part of an erodible retardant element in the layer;(e) a bacterial degradation element material to form any part of a bacterial degradation element in the layer; and (f) an excipient component material to form any part of an excipient component in the layer. In some embodiments, the method further comprises generating the layer-by-layer model of the oral drug dosage form. In some embodiments, dispensing is done by means of extrusion-melt deposition (EDM). In some embodiments, dispensing of the shell material, dispensing of the drug component material, dispensing of the pH-based enteric element material, dispensing of the erodible retardant element material, and dispensing of the shell material are each; Petition 870250088298, dated 09 / 29 / 2025, page 31 / 266 15 / 181 performed by a different print head. Extrusion and fusion deposition (MED) is a 3D printing method, as described in WO2021042865A1, WO2021164660A1, WO2022089588A1 and WO2022089631A1, which are incorporated herein in their entirety.

[0023] In another aspect, a method for treating a condition in an individual is provided in this document, the method comprising administering to the individual any oral drug dosage form described in this document. In some embodiments, the condition is selected from the group consisting of a gastrointestinal disorder, central nervous system (CNS) disorder, cardiovascular disease, hypertension, atherosclerosis, angina, arterial obstruction, peripheral arterial disease, myocardial pathology, arrhythmia, acute myocardial infarction, angina, cardiomyopathy, congestive heart failure, coronary artery disease (CAD), carotid artery disease, endocarditis, hypercholesterolemia, hyperlipidemia, peripheral arterial disease (PAD), genitourinary disorders;Erectile dysfunction, urinary tract diseases, benign prostatic hypertrophy (BPH), renal tubular acidosis, diabetic nephropathy, glomerulonephritis, glomerulosclerosis, urinary tract infection, fecal incontinence, eye disease, glaucoma, blepharitis, ocular hypertension, retinopathy, conjunctivitis, scleritis, retinitis, keratitis, corneal ulcer, iritis, chorioretinal inflammation, macular edema, xerophthalmia, lung disease, asthma, pulmonary hypertension, acute respiratory distress syndrome, COPD, emphysema, pneumonia, tuberculosis, bronchitis, acute bronchitis, bronchiectasis, bronchiolitis, bronchopulmonary dysplasia, byssinosis, coccidioidomycosis (Cocci), cystic fibrosis, influenza, lung cancer, mesothelioma, metabolic disease, hypercalciuria, hyperglycemia, hyperinsulinemic hypoglycemia, hyperinsulinism, hyperlysinuria and Hypoglycemia. In some modalities, the gastrointestinal disorder is selective; Petition 870250088298, dated 09 / 29 / 2025, page 32 / 266 16 / 181 selected from the group consisting of irritable bowel disease (IBD), irritable bowel syndrome (IBS), constipation, diarrhea, infection, and carcinoma. In some modalities, IBD is associated with Crohn's disease or ulcerative colitis. In some modalities, carcinoma is colon cancer or colorectal cancer. In some modalities, CNS disorder is selected from the group consisting of neurogenic pain, stroke, dementia, Alzheimer's disease, Parkinson's disease, neuronal degeneration, meningitis, spinal cord injury, cerebral vasospasm, and amyotrophic lateral sclerosis.

[0024] In another aspect, a method is provided in this document for providing local release of a drug in the colon of an individual, the method comprising administering to the individual any oral drug dosage form described in this document, where the individual is suffering from a gastrointestinal disorder.

[0025] In another aspect, a method is provided in this document for providing systemic release of a drug to an individual, the method comprising administering to the individual any oral drug dosage form described in this document, wherein the individual is suffering from central nervous system (CNS) disorder, cardiovascular disease, hypertension, atherosclerosis, angina, arterial obstruction, peripheral arterial disease, myocardial pathology, arrhythmia, acute myocardial infarction, angina, cardiomyopathy, congestive heart failure, coronary artery disease (CAD), carotid artery disease, endocarditis, hypercholesterolemia, hyperlipidemia, peripheral arterial disease (PAD), genitourinary disorders;Erectile dysfunction, urinary tract diseases, benign prostatic hypertrophy (BPH), renal tubular acidosis, diabetic nephropathy, glomerulonephritis, glomerulosclerosis, urinary tract infection, fecal incontinence, eye disease, glaucoma, blepharitis, ocular hypertension, retinopathy, conjunctivitis, scleritis, retinitis, keratitis; Petition 870250088298, dated 09 / 29 / 2025, page 33 / 266 17 / 181 corneal ulcer, iritis, chorioretinal inflammation, macular edema, xerophthalmia, lung disease, asthma, pulmonary hypertension, acute respiratory distress syndrome, COPD, emphysema, pneumonia, tuberculosis, bronchitis, acute bronchitis, bronchiectasis, bronchiolitis, bronchopulmonary dysplasia, byssinosis, coccidioidomycosis (Cocci), cystic fibrosis, influenza, lung cancer, mesothelioma, metabolic disease, hypercalciuria, hyperglycemia, hyperinsulinemic hypoglycemia, hyperinsulinism, hyperlysinuria or hypoglycemia.

[0026] In some embodiments, the design methods provided in this document comprise the use of one or more tracking tracks, so that external imaging techniques, for example, x-ray imaging, can be used to assess the state (such as whether erosion / release of the oral drug dosage form has not yet occurred, is undergoing erosion / release of the oral drug dosage form, or completion of erosion / release of the oral drug dosage form) of one or more components of an oral drug dosage form taught in this document in relation to the location of the oral drug dosage form in the individual to whom it was administered. For example, such tracking capabilities then allow confirmation that one or more components of an oral drug dosage form are behaving as desired, such as the release of a drug from a drug component occurring at a desired location in an individual's gastrointestinal tract.This additionally allows for methods comprising adjusting the design of an oral drug dosage form to provide the desired results. For example, if it is found that a drug component is eroding and releasing the drug at a site before the desired one (e.g., upstream of the desired site in the gastrointestinal tract), then one or more aspects of the delaying component can be adjusted accordingly. Petition 870250088298, dated 09 / 29 / 2025, page 34 / 266 18 / 181 as when altering the composition or thickness of a material thereof.

[0027] In some embodiments, a method is provided for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, wherein the oral drug dosage form comprises: a drug component comprising: a first erodible material mixed with a drug and a first erodible tracking strip; and a casing comprising a second tracking strip; a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value, wherein the pH-based enteric element comprises a third erodible tracking strip;and an erodible retardant element comprising a second erodible material, wherein the erodible retardant element comprises a fourth erodible tracking strip, wherein the pH-based enteric element, alone or in combination with the casing, prevents erosion of the erodible retardant element, and wherein the erodible retardant element, alone or in combination with the casing, prevents erosion of the drug component, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over a period of time to obtain a location of the oral drug dosage form and a state of the first erodible tracking strip, the second erodible tracking strip, the third erodible tracking strip and the fourth tracking strip;and (c) adjust the drug component and / or the delay component and / or the shell, or part thereof, based on the location and state of the first erodible tracking strip, the second erodible tracking strip, the third erodible tracking strip and the fourth tracking strip, to design the; Petition 870250088298, dated 09 / 29 / 2025, page 35 / 266 19 / 181 oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

[0028] In some embodiments, the adjustment of the delay component comprises adjusting the pH-based enteric element by altering one or more of the composition, the surface area exposed to body fluid after administration, or the thickness of the pH-based enteric element. In some embodiments, the adjustment of the delay component comprises adjusting the erodible delay element by altering one or more of the composition, the surface area exposed to body fluid after administration, or the thickness of the erodible delay element.

[0029] In some embodiments, a method is provided in this document for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, wherein the oral drug dosage form comprises: a drug component comprising: a first erodible material mixed with a drug, and a first erodible tracking strip; and an envelope; a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value;and an erodible retardant element comprising a second erodible material, wherein the pH-based enteric element, alone or in combination with the casing, prevents erosion of the erodible retardant element, and wherein the erodible retardant element, alone or in combination with the casing, prevents erosion of the drug component, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over a period of time to obtain a location of the oral drug dosage form and a state of the first erodible tracking band; and (c) adjusting the drug component and / or the; Petition 870250088298, dated 09 / 29 / 2025, page 36 / 266 20 / 181 delay component and / or the casing, or part thereof, based on the location and state of the first erodible tracking band, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

[0030] In some embodiments, the first erodible material mixed with the drug and the first erodible tracking strip are not in direct contact with each other. In some embodiments, the sheath comprises a second tracking strip, wherein the second tracking strip is configured to be imaged in order to obtain a state of the second tracking strip. In some embodiments, the adjustment is based on the location and state of the first erodible tracking strip and / or the second tracking strip. In some embodiments, the pH-based enteric element comprises a third tracking strip, wherein the third tracking strip is configured to be imaged in order to obtain a state of the third erodible tracking strip.In some embodiments, the adjustment is based on the location and state of the first erodible tracking strip, and / or the second tracking strip, and / or the third erodible tracking strip. In some embodiments, the erodible delay element comprises a fourth tracking strip, and in which the fourth tracking strip is configured to be imaged in order to obtain a state of the fourth erodible tracking strip. In some embodiments, the adjustment is based on the location and state of the first erodible tracking strip, and / or the second tracking strip, and / or the third erodible tracking strip, and / or the fourth erodible tracking strip.

[0031] In some modalities, image acquisition provides a location of the oral drug dosage form when the first erodible tracking band begins to erode. In some modalities, the Petition 870250088298, dated 09 / 29 / 2025, page 37 / 266 21 / 181 image acquisition provides a location of the oral drug dosage form when the first erodible tracking band has completely eroded. In some embodiments, the adjustment comprises adjusting the delay component, or part thereof, to increase the delay in drug release from the oral drug dosage form, based on the location and state of the first erodible tracking band showing earlier release than desired. In some embodiments, the adjustment comprises adjusting the delay component, or part thereof, to reduce the delay in drug release from the oral drug dosage form based on the location and state of the first erodible tracking band showing later release than desired.

[0032] In some embodiments, the first tracking strip comprises barium sulfate. In some embodiments, imaging comprises x-ray imaging. In some embodiments, the method further comprises obtaining one or more pharmacokinetic (PK) parameters associated with the drug after administration of the oral drug dosage form to an individual. In some embodiments, the method further comprises identifying a relationship between one or more PK parameters and the location and state information of the first tracking strip. In some embodiments, the method further comprises adjusting the drug component and / or the delay component, or part thereof, based on the relationship between one or more PK parameters and the location and state information of the first tracking strip. In some embodiments, imaging does not involve a magnetism-based technique or an invasive imaging technique.

[0033] In some embodiments, a method is provided in this document for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in Petition 870250088298, dated 09 / 29 / 2025, page 38 / 266 22 / 181 an individual, wherein the oral drug dosage form comprises: a drug component comprising a first erodible material mixed with a drug; a shell; and a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value; and an erodible delay element comprising a second erodible material, wherein the pH-based enteric element prevents erosion of the erodible delay element, and wherein the erodible delay element prevents erosion of the drug component, wherein the oral drug dosage form comprises at least one tracking strip positioned in a component thereof, the method comprising: (a) administering the oral drug dosage form to an individual;(b) obtain images of the individual over a period of time to obtain a site of the oral drug dosage form and a state of at least one tracking band; and (c) adjust the drug component and / or delay component and / or coating, or part thereof, based on the site and state of at least one tracking band, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

[0034] In some embodiments, one of the tracking bands is located on, or near, the drug component. In some embodiments, the tracking bands are located on the shell. In some embodiments, one of the tracking bands is located on the pH-based enteric element. In some embodiments, one of the tracking bands is located on the erodible retardant element. In some embodiments, at least one of the tracking bands is erodible. Petition 870250088298, dated 09 / 29 / 2025, p. 39 / 266 23 / 181

[0035] In some embodiments, a method is provided in this document for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, wherein the oral drug dosage form comprises: a drug component comprising a first erodible material mixed with a drug; and a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value;and an erodible delay element comprising a second erodible material, wherein the pH-based enteric element prevents erosion of the erodible delay element, and wherein the erodible delay element prevents erosion of the drug component, wherein the oral drug dosage form comprises at least one tracking strip positioned on a component thereof, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over a period of time to obtain a location of the oral drug dosage form and a state of at least one tracking strip; and (c) adjusting the drug component and / or delay component, or part thereof, based on the location and state of at least one tracking strip, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

[0036] In some embodiments, one of the tracking bands is located on, or near, the drug component. In some embodiments, one of the tracking bands is located on the pH-based enteric element. In some embodiments, one of the tracking bands is located on the erodible delay element. In some embodiments, at least one of the tracking bands is erodible. Petition 870250088298, dated 09 / 29 / 2025, p. 40 / 266 24 / 181

[0037] In some aspects, a method for treating ulcerative colitis is provided in this document, the method comprising administering to a human subject an oral drug dosage form according to any of claims 1 to 84, wherein the oral drug dosage form comprises a JAK inhibitor. In some embodiments, the JAK inhibitor comprises tofacitinib. In some embodiments, the oral drug dosage form comprises about 11 mg or less of tofacitinib. In some embodiments, the oral drug dosage form comprises about 5.5 mg or less of tofacitinib. In some embodiments, the oral drug dosage form is administered once daily.

[0038] It will also be understood by those skilled in the art that alterations in the form and details of the implementations described in this document can be made without departing from the scope of this invention. Furthermore, although various advantages, aspects, and objects have been described with reference to various implementations, the scope of this invention should not be limited by reference to such advantages, aspects, and objects.

[0039] All references cited in this document, including patent applications and publications, are incorporated in full. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] FIGS. 1A-1K show cross-sectional diagrams of exemplary oral drug dosage forms provided in this document.

[0041] FIG. 2 shows an exemplary oral drug dosage form provided in this document, including several cross-sectional diagrams thereof.

[0042] FIG. 3 shows an exemplary oral drug dosage form provided in this document, including several cross-sectional diagrams thereof. Petition 870250088298, dated 09 / 29 / 2025, p. 41 / 266 25 / 181

[0043] FIG. 4 shows an exemplary oral drug dosage form provided in this document, including several cross-sectional diagrams thereof.

[0044] FIG. 5 shows an in vitro dissolution profile of an exemplary oral drug dosage form provided in this document (see Tables 1A and 1B and FIG. 2) with an overlay of the erosion of certain components present in it, including a set of tracking bands. For each time series of the dissolution profile, the numerical data are based on the average of four measurements and the standard deviation is provided using error bars. The in vitro lag time of the oral drug dosage form is approximately 4.5 hours.

[0045] FIG. 6A shows an in vitro dissolution profile of an exemplary oral drug dosage form provided in this document (see Tables 2A and 2B and FIG. 3) with an overlay of the erosion of certain components present in it, including a set of tracking bands. For each time series of the dissolution profile, the numerical data are based on the average of three measurements and the standard deviation is provided using error bars. The in vitro lag time of the oral drug dosage form is approximately 4 hours. FIG. 6B shows photographs taken during the dissolution process.

[0046] FIG. 7 shows an in vitro dissolution profile of an exemplary oral drug dosage form provided in this document (see Tables 3A and 3B and FIG. 4). For each time series of the dissolution profile, the numerical data is based on the average of three measurements and the standard deviation is provided using error bars. The in vitro lag time of the oral drug dosage form is approximately 4.5 hours.

[0047] FIG. 8 shows an in vitro dissolution profile of an exemplary oral drug dosage form provided in this document (see Petition 870250088298, dated 09 / 29 / 2025, p. 42 / 266 26 / 181 Tables 4A and 4B and FIG. 4) with an overlay of the erosion of certain components present in it, including a set of tracking bands. For each time series of the dissolution profile, the numerical data are based on the average of three measurements and the standard deviation is provided using error bars. The in vitro lag time of the oral drug dosage form is approximately 5 hours.

[0048] FIGS. 9A and 9B show pharmacokinetic (PK) graphs of a reference (Xeljanz XR) and of exemplary oral drug dosage forms provided in this document.

[0049] FIGS. 10A-10C show time series x-ray images of beagle dogs after administration of exemplary oral drug dosage forms provided in this document. Annotations are provided to indicate the oral drug dosage form and to provide status information such as drug release onset and drug release completion.

[0050] FIG. 11 shows an exemplary oral drug dosage form provided in this document, including several cross-sectional diagrams thereof.

[0051] FIGS. 12A-12D show the in vitro dissolution profiles of the exemplary oral drug dosage forms provided in this document (see Tables 5A-8B and FIG. 11). For each dissolution profile time series, the numerical data are based on the average of five measurements and the standard deviation is provided using error bars.

[0052] FIG. 13 shows pharmacokinetic (PK) plots of a reference (Xeljanz XR) and exemplary oral drug dosage forms provided in this document.

[0053] FIGS. 14A-14C show time series x-ray images of beagle dogs after administration of exemplary oral drug dosage forms provided in this document. The annotations Petition 870250088298, dated 09 / 29 / 2025, page 43 / 266 27 / 181 are provided to indicate the oral drug dosage form and to provide status information, such as drug release onset and drug release completion.

[0054] FIG. 15 shows pharmacokinetic (PK) graphs measured from healthy volunteers of a reference (Xeljanz XR) and exemplary oral drug dosage forms provided in this document.

[0055] FIG. 16 shows time series x-ray images of healthy volunteers after administration of exemplary oral drug dosage forms provided in this document. Annotations are provided to indicate the oral drug dosage form and to provide state information such as drug release onset and drug release completion. DETAILED DESCRIPTION

[0056] In some aspects, an oral drug dosage form is provided in this document, configured to release a drug at a desired location in an individual's colon, the oral drug dosage form comprising: a drug component comprising an erodible material mixed with the drug; and a delay component not mixed with the drug, wherein the delay component is configured to prevent the release of the drug from the drug component until the oral drug dosage form reaches the individual's colon after administration, and wherein the delay component comprises: a pH-based enteric element comprising an erodible material configured to erode at or above a predetermined pH value. In some embodiments, the oral drug dosage form is configured so that essentially all of the drug, for example, 100%, in the oral drug dosage form is released into an individual's colon. Petition 870250088298, dated 09 / 29 / 2025, p. 44 / 266 28 / 181

[0057] The oral drug dosage forms described in this document are based on the inventors' unique insights and findings regarding the design and production of oral drug dosage forms for precise drug release in the colon of the gastrointestinal tract. As taught and demonstrated in this document, in certain aspects, the oral drug dosage forms are capable of achieving complete drug release in the colon (including complete release in a specific area of ​​the colon), which allows maximizing the therapeutic efficacy of certain drugs while minimizing side effects caused by drug release in another area of ​​the gastrointestinal tract. For example, this toxicity can occur when there is unwanted systemic absorption due to drug release in another area of ​​the gastrointestinal tract.The colon is susceptible to a variety of pathological conditions, including inflammatory bowel disease, irritable bowel syndrome, constipation, diarrhea, infections, and carcinoma. The oral drug dosage forms taught in this document are, in certain respects, capable of effectively delivering a drug to the site of a pathological condition, namely the colon, to provide effective local therapy. Furthermore, in other respects, the colon is a site in the gastrointestinal tract that provides the potential for effective absorption and thus systemic release. For example, the colon has comparatively lower levels of several luminal and mucosal metabolic enzymes (e.g., proteases) and transporters, which confers therapeutic advantages for certain drugs that would otherwise not be absorbed into the systemic circulation if released elsewhere in the gastrointestinal tract.For example, lower proteolytic activity in the colon may be beneficial for the release of biological products (e.g., peptides, proteins, monoclonal antibodies, nucleic acids, and vaccines). The capacity of the oral drug dosage forms taught. Petition 870250088298, dated 09 / 29 / 2025, page 45 / 266 29 / 181 in this document to promote complete release in the colon (including release in a specific area of ​​the colon) represents a significant advance in the field of drug delivery, for both local and systemic therapies.

[0058] An illustrative example of the usefulness of certain oral drug dosage forms provided in this document can be found in the oral drug dosage forms described herein, which are configured with a drug for the treatment of ulcerative colitis. Ulcerative colitis is a condition that affects a specific area of ​​the gastrointestinal tract, namely, ulcerative colitis causes inflammation and ulcers in the innermost layer of the large intestine (colon) and rectum. Known agents, such as anti-inflammatory drugs including JAK inhibitors, are effective in treating an individual with ulcerative colitis by reducing inflammation and ulcer formation. However, conventional drug dosage forms comprising these drugs have demonstrated limitations, such as incomplete drug release at the site of need.This release outside the colon reduces the effectiveness of these conventional oral drug dosage forms and can lead to systemic toxicity. The advantages of the oral drug dosage forms described in this document provide a significant improvement in the treatment of conditions such as ulcerative colitis.

[0059] Traditionally, the oral release of biological products, such as peptides, proteins, monoclonal antibodies, and nucleic acids (e.g., RNA / ) is limited due, at least partially, to the presence of digestive enzymes in the gastrointestinal tract. Vaccines can also face high levels of degradation due to phagocytosis rates. The lower level of functional proteolytic enzymes, functional pancreatic digestive enzymes, and phagocytosis in the colon, in comparison Petition 870250088298, dated 09 / 29 / 2025, page 46 / 266 30 / 181 interaction with other areas of the gastrointestinal tract represents an opportunity if these biological agents can be safely released into the colon. In certain aspects, the oral drug dosage forms taught in this document can protect a biological drug until its release in the colon, thus providing a significant advance in the oral delivery of these therapeutic agents.

[0060] Therefore, in certain respects, an oral drug dosage form is provided in this document, configured to release a drug at a desired location in an individual's colon, the oral drug dosage form comprising: a drug component comprising an erodible material mixed with the drug; and a delay component not mixed with the drug, wherein the delay component is configured to prevent the release of the drug from the drug component until the oral drug dosage form reaches the individual's colon after administration, wherein the delay component comprises: a pH-based enteric element comprising an erodible material configured to erode at or above a predetermined pH value.In some embodiments, the delay component further comprises an erodible delay element, wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible delay element. In some embodiments, the oral drug dosage form further comprises a second drug. In some embodiments, the oral drug dosage form further comprises a bacterial degradation portion. In some embodiments, the delay component further comprises a bacterial degradation element comprising an erodible material mixed with the bacterial degradation portion. In some embodiments, the delay component does not comprise an erodible delay element. In some embodiments, a. Petition 870250088298, dated 09 / 29 / 2025, page 47 / 266 31 / 181 Oral drug dosage form does not comprise a shell. In some embodiments, the oral drug dosage form additionally comprises a shell not mixed with the drug, wherein the oral drug dosage form is configured so that the shell, or a part thereof, and the delay element prevent erosion of the drug component.

[0061] In other respects, a commercial lot of any oral drug dosage form described herein is provided in this document, wherein the commercial lot has a standard deviation of about 0.05 or less for each of the following: a quantity of a drug in the oral drug dosage form; a weight of the oral drug dosage form; a maximum transverse dimension of the oral drug dosage form; and a transverse dimension perpendicular to the maximum transverse dimension of the oral drug dosage form. In some embodiments, the commercial lot comprises at least about 1000 of the oral drug dosage forms.

[0062] In other respects, a method for three-dimensional (3D) printing of any oral drug dosage form described herein is provided in this document, the method comprising dispensing materials according to a layer-by-layer model of the oral drug dosage form to print the oral drug dosage form, wherein each layer of the layer-by-layer model is printed by dispensing, as required, a layer of: (a) a shell material to form any part of a shell in the layer; (b) a drug component material to form any part of a drug component in the layer; (c) a pH-based enteric element material to form any part of a pH-based enteric element in the layer; (d) an erodible retardant element material to form any part of an erodible retardant element in the layer; (e) an element material of Petition 870250088298, dated 09 / 29 / 2025, page 48 / 266 32 / 181 bacterial degradation to form any part of a bacterial degradation element in the layer; and (f) an excipient component material to form any part of an excipient component in the layer.

[0063] In other respects, a method for treating a condition in an individual is provided in this document, the method comprising administering to the individual an oral drug dosage form described in this document.

[0064] In other respects, a method is provided in this document for providing local release of a drug in the colon of an individual, the method comprising administering to the individual an oral drug dosage form described in this document.

[0065] In other respects, a method for providing systemic delivery of a drug to an individual is provided in this document, the method comprising administering to the individual an oral drug dosage form described in this document. I. Definitions

[0066] For the purposes of interpreting this descriptive report, the following definitions shall apply and, where appropriate, terms used in the singular shall also include the plural and vice versa. In the event that any definition set forth below conflicts with any document incorporated herein by reference, the definition set forth below shall prevail.

[0067] The terms “peptide” and “protein,” as used in this document, may be used interchangeably to refer to a polymer comprising amino acid residues, and are not limited to a minimum length. Such polymers may contain natural or non-natural amino acid residues, or combinations thereof, and include, among others, peptides, oligopeptides, dimers, trimers, and Petition 870250088298, dated 09 / 29 / 2025, p. 49 / 266 33 / 181 multimers of amino acid residues. Peptides or full-chain proteins, and fragments thereof, are encompassed by this definition. The terms also include modified species thereof, for example, post-translational modifications of one or more residues, for example, methylation, phosphorylation, glycosylation, sialylation or acetylation.

[0068] As used in this document, the term “tofacitinib” includes, unless otherwise indicated, any pharmaceutically acceptable form and salts thereof. In some embodiments, tofacitinib may be present in crystalline form. In some embodiments, tofacitinib may be present in amorphous form. In some embodiments, the pharmaceutically acceptable form is any pharmaceutically acceptable form, including solvates, hydrates, isomorphs, polymorphs, cocrystals, pseudomorphs, neutral forms, acid-addition salt forms and prodrugs.In some embodiments, the pharmaceutically acceptable form is a pharmaceutically acceptable salt. Conventional concentration and recrystallization techniques can be employed in the generation and isolation of pharmaceutically acceptable salts of a JAK inhibitor, including the use of acids such as acetic acid, lactic acid, succinic acid, maleic acid, tartaric acid, citric acid, gluconic acid, ascorbic acid, mesylic acid, tosylic acid, benzoic acid, cinnamic acid, fumaric acid, sulfuric acid, phosphoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfamic acid, sulfonic acid, such as methanesulfonic acid, benzenesulfonic acid, and related acids. In some embodiments, tofacitinib is tofacitinib citrate.

[0069] As used in this document, the use of the terms “treat”, “treatment”, “treating” or equivalents thereof, refers to an approach to obtain beneficial or desired results, including a reduction in the symptoms of, for example, a disease. For the purposes of this invention, beneficial or desired clinical results include, en. Petition 870250088298, dated 09 / 29 / 2025, p. 50 / 266 34 / 181 among others, one or more of the following: relieve one or more symptoms resulting from the disease, reduce the severity of one or more symptoms resulting from the disease, prevent the increase in the severity of one or more symptoms resulting from the disease, decrease the dose of one or more other medications needed to treat and / or control the disease, and improve quality of life.

[0070] As used in this document, the term “individual” refers to a mammal and includes, among others, humans, cattle, horses, cats, dogs, rodents, rats, mice, dogs, or primates. In some modalities, the individual is a human individual.

[0071] The terms “comprising”, “having”, “containing”, and “including”, as well as other similar and grammatically equivalent forms thereof, as used in this document, are intended to be equivalent in meaning and to be open-ended in the sense that an item or items following any of these words are not intended to be an exhaustive list of such item or items, nor to be limited only to the item or items listed. For example, an item “comprising” components A, B, and C may consist of (i.e., contain only) components A, B, and C, or it may contain not only components A, B, and C, but also one or more other components. Therefore, it is understood and understood that “comprising” and similar forms thereof, as well as grammatically equivalent forms thereof, include the invention of modalities of “essentially consisting of” or “consisting of”.

[0072] As used in this document, the term “semi-solid” and other similar forms, and grammatical equivalents thereof, refer to a viscous liquid that can flow under external forces (pressure, buoyancy, rotational force, gravity, etc.) or under process conditions (temperature, pressure, etc.).

[0073] When a range of values ​​is given, it is understood that each intermediate value, up to the tenth of a unit of the lower limit, is Petition 870250088298, dated 09 / 29 / 2025, p. 51 / 266 35 / 181 unless the context clearly indicates otherwise, between the upper and lower limits of that range and any other stated or intermediate value within that stated range, is encompassed in the invention, subject to any limit specifically excluded in the stated range. Where the stated range includes one or both limits, ranges that exclude one or both of the included limits are also encompassed in the invention.

[0074] The reference to “about” a value or parameter in this document includes (and describes) variations that are directed to that value or parameter itself. For example, the description referring to “about X” includes the description of “X”.

[0075] As used in this document, including in the attached claims, the singular forms “a / an”, “or” and “the” include plural referents, unless the context clearly indicates otherwise.

[0076] Persons skilled in the art will recognize that various embodiments are possible within the scope and spirit of the present invention. The following description illustrates the invention and, however, should not be construed in any way as a limitation on the scope of the inventions described herein. II. Oral drug dosage forms

[0077] In some aspects, an oral drug dosage form is provided that is configured to release a drug at a desired site in the colon. As described in this document, in some embodiments, the oral drug dosage form configured to release a drug at a desired site in an individual's colon comprises: a drug component comprising an erodible material mixed with the drug; and a delay component not mixed with the drug, wherein the delay component is configured to prevent the release of the drug from the drug component until the dosage form of Petition 870250088298, dated 09 / 29 / 2025, page 52 / 266 36 / 181 Oral drug dosage form reaches the individual's colon after administration, and wherein the delay component comprises: a pH-based enteric element comprising an erodible material configured to erode at or above a predetermined pH value. In some embodiments, the oral drug dosage form has one or more additional features, for example, an erodible delay element, a second drug and, optionally, a second drug component, a bacterial degradation portion and, optionally, a bacterial degradation element, a shell or an excipient. The oral drug dosage forms described in this document may comprise a variety of combinations of the components described in this document and may be arranged in a variety of configurations.In some examples, such as those provided in the section below, components and configurations are described in a modular manner, and such description is not intended to limit the scope of oral drug dosage forms encompassed in this document. A. Exemplary oral drug dosage forms

[0078] For the purposes of illustrating and explaining the subject matter provided in this document, certain oral drug dosage forms covered in this document are described in detail below.

[0079] Exemplary cross-sectional schematic diagrams of oral drug dosage forms configured to release a drug at a desired site in the colon are provided in FIGS. 1A-1H. As illustrated in FIG. 1A, in some embodiments, the oral drug dosage form 100 comprises a drug component 102 comprising an erodible material mixed with a drug; and a delay component not mixed with the drug, wherein the delay component is configured to prevent the release of the drug from the drug component until the drug dosage form Petition 870250088298, dated 09 / 29 / 2025, page 53 / 266 37 / 181 oral reaches the individual's colon after administration, and wherein the delay component comprises an enteric-based element with a pH of 104 comprising an erodible material configured to erode at or above a predetermined pH value. After administration, the outer surfaces, which constitute the enteric-based element with a pH of 104, are exposed to the individual's gastrointestinal fluid. Once a pH threshold is reached, for example, based on a pH in or near the colon, or in a part thereof, the material on the surfaces of the pH 104 enteric-based element erodes from the oral drug dosage form, as shown by the direction of arrows 106, 108, 110 and 112. Based on the design of the pH 104 enteric-based element, the drug component 102, or parts thereof (such as surfaces), can be exposed in a controlled manner to gastrointestinal fluid to control drug release from the oral drug dosage form 100.For example, by having a thinner thickness (as assessed along the erosion direction and compared, for example, to the lateral thicknesses) of the pH 104 enteric-based element above and below the drug component 102, the erosion of the pH 104 enteric-based element will first expose an upper surface 114 and a lower surface 116 of the drug component 102. The drug mixed with the drug component 102 can then be released from the oral drug dosage form 100, such as by erosion. The ability to design which aspect(s) of the drug component 102 is / are exposed to the gastrointestinal fluid enables, at least partially, a controlled release of the drug from the oral drug dosage form 100.

[0080] As illustrated in FIG. 1B, in some embodiments, the delay component additionally comprises an erodible delay element 204 not mixed with the drug. After administration, the outer surfaces of the oral drug dosage form 200, Petition 870250088298, dated 09 / 29 / 2025, page 54 / 266 38 / 181, which constitutes the pH 202 enteric-based element, are exposed to the gastrointestinal fluid in the individual. Once a pH threshold is reached, for example, based on a pH in or near the colon, or a part thereof, the material on the surfaces of the pH 202 enteric-based element erodes from the oral drug dosage form 200, as shown by the direction of arrows 208 and 210. Based on the design of the pH 202 enteric-based element, the erodible delay element 204, or parts thereof (such as surfaces), can be exposed in a controlled manner to the gastrointestinal fluid. Based on exposure to the gastrointestinal fluid, the erodible delay element 204 will erode accordingly, and then aspects of the drug component 206 will be exposed to the gastrointestinal fluid, thus providing drug release from the oral drug dosage form 100.The design of the delay component may expose certain aspects of the drug component 206, such as allowing, at least partially, a controlled-release drug profile of the oral drug dosage form 200 to be obtained.

[0081] As illustrated in FIGS. 1C and 1D, in certain respects, the oral drug dosage forms provided in this document, for example, 300 and 400, comprise more than one component, for example, drug components. These dosage forms may be designed for sequential erosion (or at least partially sequential erosion), for example, as shown for the drug components in FIG. 1C, or compartment-based erosion, for example, as shown for the drug components in FIG. 1D. Specifically, as illustrated in FIG. 1C, after administration, the outer surfaces of the oral drug dosage form 300, which constitute the pH 302-based enteric element, are exposed to the individual's gastrointestinal fluid. Once a pH threshold is reached, for example, based on a pH at or near Petition 870250088298, dated 09 / 29 / 2025, page 55 / 266 39 / 181 of the colon, or a part thereof, the material on the surfaces of the pH 302 enteric-based element erodes from the oral drug dosage form, as shown by the direction of arrows 310 and 312. Based on the design of the pH 302 enteric-based element, the erodible retardant element 304, or parts thereof (such as surfaces), can be exposed in a controlled manner to gastrointestinal fluid. Based on exposure to gastrointestinal fluid, the erodible delay element 304 will erode accordingly, and then aspects of the second drug component 306 will be exposed to the gastrointestinal fluid, thus providing a release of a second drug from the oral drug dosage form 300. Based on exposure to gastrointestinal fluid, the second drug component 306 will erode accordingly, and then aspects of the drug component 308 will be exposed to the gastrointestinal fluid, thus providing the release of the drug from the oral drug dosage form 300.The design of the delay component may expose certain aspects of the second drug component 306 so that a controlled-release profile of the second drug of the oral drug dosage form 300 is obtained. The design of the delay component and / or the second drug component 306 may expose certain aspects of the drug component 308 so that a controlled-release profile of the drug of the oral drug dosage form 300 is obtained. The drug and the second drug may be the same or different. In some embodiments, an intermediate material is positioned between at least part of the second drug component 306 and the drug component 308, such as an erodible second delay element.

[0082] As illustrated in FIG. 1 D, a compartment-based approach can be adopted to design an oral drug dosage form 400 taught in this document. After administration, the outer surfaces of the oral drug dosage form 400, which Petition 870250088298, dated 09 / 29 / 2025, page 56 / 266 40 / 181 constitutes the enteric-based element with pH 402, and is exposed to gastrointestinal fluid in the individual. Once a pH threshold is reached, for example, based on a pH in or near the colon, or a part thereof, the material on the surfaces of the enteric-based element with pH 402 erodes from the oral drug dosage form 400, as shown by the direction of arrows 410 and 412. Based on the design of the enteric-based element with pH 402, the erodible retardant element 404, or parts thereof (such as surfaces), can be exposed in a controlled manner to gastrointestinal fluid. Based on exposure to gastrointestinal fluid, the erodible delay element 404 will erode accordingly, and then aspects of the drug component 406 and the second drug component 408 will be exposed to the gastrointestinal fluid, thus providing the release of the drug and a second drug, respectively, from the oral drug dosage form 400.The design of the delay component can control drug release, such as achieving, for example, separate drug release, simultaneous drug release, or partially overlapping drug release. In some embodiments, a second erodible delay element is associated with the second drug component 408, such that the second drug component 408 does not depend on the erodible delay element 404 for drug release. As described in this document, oral drug dosage forms may contain many compartments containing the drug and / or other aspects of the oral drug dosage form, for example, a bacterial degradation moiety and / or an excipient.

[0083] As described in this document, certain other components may be formulated in the oral drug dosage forms provided in this document, for example, a bacterial degradation moiety (such as mixed into a bacterial degradation element) and an excipient. For example, as illustrated in Petition 870250088298, dated 09 / 29 / 2025, page 57 / 266 41 / 181 FIG. 1E, after administration, the outer surfaces of the oral drug dosage form 500, which constitute the pH-based enteric element 502, are exposed to the gastrointestinal fluid in the individual. Once a pH threshold is reached, for example, based on a pH in or near the colon, or a part thereof, the material on the surfaces of the pH-based enteric element 502 erodes from the oral drug dosage form 500, as shown by the direction of arrows 510 and 512. Based on the design of the pH-based enteric element 502, the erodible retardant element 504, or parts thereof (such as surfaces), can be exposed in a controlled manner to the gastrointestinal fluid. Based on exposure to the gastrointestinal fluid, the erodible retardant element 504 will erode correspondingly, and then aspects of the bacterial degradation element mixed with a bacterial degradation portion 506 will be exposed to the gastrointestinal fluid.The bacterial degradation element 506 is then degraded to expose aspects of the drug component 508, thus providing a drug release from the oral drug dosage form 500. The design of the delay component (in FIG. 1E, the delay component comprises the pH-based enteric element 502, the erodible delay element 504, and the bacterial degradation element 506) can expose certain aspects of the drug component 508 so that a controlled drug release profile from the oral drug dosage form 500 is obtained.

[0084] In some respects, the oral drug dosage forms provided in this document comprise a shell. As illustrated in FIGS. 1F-1H, the oral drug dosage form 600 is configured to release a drug at a desired site in the colon, the oral drug dosage form comprising: a drug component comprising a first erodible material mixed with a drug; a shell not mixed with the drug, wherein the Petition 870250088298, dated 09 / 29 / 2025, page 58 / 266 42 / 181 The casing is associated with at least part of the drug component, such as by means of one or more sides of the drug component; and a retarding component not mixed with the drug, the retarding component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value; and an erodible retarding element comprising an erodible material. As discussed in more detail below and shown in FIG. 1F, the retarding component comprises a pair of layers of the pH-based enteric element and a pair of layers of the erodible retarding element that delimit the drug component, wherein the pH-based enteric element and the casing prevent erosion of the erodible retarding element, and wherein the erodible retarding element and the casing prevent erosion of the drug component.

[0085] A cross-sectional diagram of an oral drug dosage form 600 is provided in FIG. 1F. The oral drug dosage form 600 comprises a shell 602 comprising an insulating material impermeable to body fluids and a drug component 604 comprising a first erodible material mixed with a drug. As illustrated in FIG. 1F, the drug component 604 forms a layer comprising an upper surface 606, a lower surface 608 and one or more sides, for example, 610, wherein one or more sides of the drug component layer are associated with, such as in direct contact with, the shell. The use of directional terms such as upper, lower and sides is intended to facilitate the description of the invention provided herein and should not be construed as limiting the inventions from the scope provided herein.The delay component of the oral drug dosage form 600 is not mixed with the drug, and the delay component comprises: an enteric-based pH-configured element. Petition 870250088298, dated 09 / 29 / 2025, page 59 / 266 43 / 181 to erode at or above a predetermined pH value; and an erodible retarding element comprising an erodible material, wherein the pH-based enteric element and the casing prevent erosion of the erodible retarding element, and wherein the erodible retarding element and the casing prevent erosion of the drug component. Specifically, in the oral drug dosage form 600 of FIG. 1F, the retarding component comprises a pair of layer sets of a first layer of the erodible retarding element 612, a first layer of the pH-based enteric element 618, a second layer of the erodible retarding element 622 and a second layer of the pH-based enteric element 624.The oral drug dosage form 600 is configured such that the upper surface 606 of the drug component layer 604 is in direct contact with a lower surface 614 of the first layer of the erodible retardant element 612, and an upper surface 616 of the first layer of the erodible retardant element 612 is in direct contact with a lower surface 620 of the first layer of the pH-based enteric element 618. The second set of retardant component layers is similarly arranged, specifically, the lower surface 608 of the drug component layer 604 is in direct contact with the second layer of the erodible retardant element 622, and the second layer of the erodible retardant element 622 is in direct contact with the second layer of the pH-based enteric element 624. As shown in FIG.1F, the enteric-based element with pH 618, 624 and the shell 602 completely surround the erodible retardant element 612, 622 and the drug component 604.

[0086] The oral drug dosage form 600 of FIG. 1F is configured so that, when administered to a human subject, the oral drug dosage form begins a journey through the human subject's gastrointestinal system, and once the form of Petition 870250088298, dated 09 / 29 / 2025, page 60 / 266 44 / 181 oral drug dosage form 600 is subjected to a gastrointestinal fluid with a suitable pH value, such as a pH value of 5.5 or higher, an upper surface 622 of the first layer of the enteric base layer with pH 618 and a lower surface 626 of the second layer of the enteric base layer with pH 624 erode from the oral drug dosage form 600 in the direction of the respective arrows 628, 630. As shown in FIG. 1G, at a certain time after administration to the human subject, the first and second layers of the pH-based enteric element (618 and 624, as shown in FIG. 1F) eroded from the oral drug dosage form 600 and exposed the upper surface 616 of the first layer of the erodible lag element 612 and the lower surface 632 of the second layer of the erodible lag element 622 to a gastrointestinal fluid.The first and second layers of the erodible retardant element erode from the oral drug dosage form 600 in the direction of the respective arrows 634, 636. As shown in FIG. 1H, at a certain time after administration to the human subject, the first and second layers of the erodible retardant element (612 and 622, as shown in FIG. 1F and 1G) eroded from the oral drug dosage form 600 and exposed the upper surface 606 and lower surface 608 of the drug component 604, and the drug is released from the oral drug dosage form by means of erosion of the drug component 604, such as in the direction of arrows 638, 640. In some embodiments, the drug component breaks apart and at least a portion of the drug component may be released from the oral drug dosage form and additionally erode to release the drug into the human subject.

[0087] As described in this document, certain other components may be formulated in the oral drug dosage forms provided in this document, for example, a portion of Petition 870250088298, dated 09 / 29 / 2025, page 61 / 266 45 / 181 bacterial degradation (such as mixed in a bacterial degradation element) and an excipient. For example, as illustrated in FIG. 11. The oral drug dosage form 700 comprises a shell 702 comprising an insulating material impermeable to body fluids and a drug component 704 comprising a first erodible material mixed with a drug. As illustrated in FIG. 11, the drug component 704 forms a layer comprising an upper surface 706, a lower surface 708 and one or more sides, for example, 710, wherein one or more sides of the drug component layer are associated with, such as in direct contact with, the shell. The use of directional terms such as upper, lower and sides is intended to facilitate the description of the invention provided herein and should not be construed as limiting the scope of the inventions provided herein.Bacterial degradation elements 732 and 734 are then degraded to expose aspects of the drug component 706 and 708, thus providing drug release from the oral drug dosage form 700. The delay component of the oral drug dosage form 700 is not mixed with the drug, and the delay component comprises: a pH-based enteric element configured to erode at or above a predetermined pH value; and an erodible delay element comprising an erodible material, wherein the pH-based enteric element and the casing prevent erosion of the erodible delay element, and wherein the erodible delay element and the casing prevent erosion of the drug component. Specifically, in the oral drug dosage form 700 of FIG.11, the retardant component comprises a pair of layer sets of a first layer of the erodible retardant element 712, a first layer of the pH-based enteric element 718, a second layer of the erodible retardant element 722 and a second layer of the enteric-based element. Petition 870250088298, dated 09 / 29 / 2025, p. 62 / 266 46 / 181 of pH 724. The oral drug dosage form 700 is configured so that the upper surface 706 of the drug component layer 704 is in direct contact with a lower surface 714 of the first layer of the erodible retardant element 712, and an upper surface 716 of the first layer of the erodible retardant element 712 is in direct contact with a lower surface 720 of the first layer of the enteric-based element of pH 718. The second set of retardant component layers is similarly arranged, specifically, the lower surface 708 of the drug component layer 704 is in direct contact with the second layer of the erodible retardant element 722, and the second layer of the erodible retardant element 722 is in direct contact with the second layer of the enteric-based element of pH 724. As shown in FIG.11, the enteric element based on pH 718, 724 and the shell 702 completely surround the erodible retardant element 712, 722, the bacterial degradation element 732, 734 and the drug component 704.

[0088] This descriptive report provides additional formats of oral drug dosage forms. For example, as illustrated in FIG. 1J. Oral drug dosage form 800 comprises a shell 802 comprising an insulating material impermeable to body fluids and a drug component 804 comprising a first erodible material mixed with a drug. As illustrated in FIG. 1J, the drug component 804 forms a layer comprising an upper surface 806, a lower surface 808 and one or more sides, for example, 810, wherein one or more sides of the drug component layer are associated with, such as in direct contact with, the shell. The use of directional terms such as upper, lower and sides is intended to facilitate the description of the invention provided herein and should not be construed as limiting the scope of the inventions provided herein. Petition 870250088298, dated 09 / 29 / 2025, p. 63 / 266 47 / 181 The bacterial degradation element 832 is then degraded to expose aspects of the drug component 806 and 808, thus providing a release of the drug from the oral drug dosage form 800. The delay component of the oral drug dosage form 800 is not mixed with the drug, and the delay component comprises: an enteric pH-based element configured to erode at or above a predetermined pH value; and an erodible delay element comprising an erodible material, wherein the enteric pH-based element and the casing prevent erosion of the erodible delay element, and wherein the erodible delay element and the casing prevent erosion of the drug component. Specifically, in the oral drug dosage form 800 of FIG.1J, the delay component comprises a pair of layer sets of a first layer of the erodible delay element 812, a first layer of the pH-based enteric element 818, a second layer of the erodible delay element 822 and a second layer of the pH-based enteric element 824. The oral drug dosage form 800 is configured such that the upper surface 806 of the drug component layer 804 is in direct contact with a lower surface 814 of the first layer of the erodible delay element 812, and an upper surface 816 of the first layer of the erodible delay element 812 is in direct contact with a lower surface 820 of the first layer of the pH-based enteric element 818.The second set of layers of the delay components is arranged similarly, specifically, the lower surface 808 of the drug component layer 804 is in direct contact with the second layer of the erodible delay element 822, and the second layer of the erodible delay element 822 is in direct contact with the second layer of the pH-based enteric element 824. As shown in FIG. 1J, the pH-based enteric element 818, 824 and the casing 802 surround. Petition 870250088298, dated 09 / 29 / 2025, page 64 / 266 48 / 181 completely the erodible retardant element 812, 822, the bacterial degradation element 832 and the drug component 804. In some embodiments, the oral drug dosage form is configured so that the drug component is released from the oral drug dosage form at some point after administration, for example, after erosion of another component of the drug dosage form, such as the bacterial degradation element. In these embodiments, the release of the drug from the drug component will consider, for example, the surface area of ​​the drug component exposed to a gastrointestinal fluid.

[0089] In certain respects, the oral drug dosage forms provided in this document comprise a first enteric pH-based element and a second enteric pH-based element. As illustrated in FIG. 1K, after administration, the outer surfaces of the oral drug dosage form 900, which constitute the first enteric pH-based element 902, are exposed to the gastrointestinal fluid in the individual. Once the pH threshold is reached, for example, based on or above a pH value of about 5.5, or a portion thereof, the material of the first enteric pH-based element 902 erodes from its surface, as shown by the direction of arrows 910 and 912. Based on the design of the first enteric pH-based element 902, gastric juice can be prevented from penetrating the oral drug dosage form 900.Then, once the second pH limit is reached, for example, based on a pH in or near the colon, or a part thereof, the material on the surfaces of the second enteric-based element with pH 906 will erode from the oral drug dosage form 900. Based on the design of the second enteric-based element with pH 906, drug release in the small intestine can be prevented. Based on the design of the first enteric-based element with pH 902 and the second enteric-based element with pH 906, the... Petition 870250088298, dated 09 / 29 / 2025, pp. 65 / 266 49 / 181 erodible delay element 904, or parts thereof (such as surfaces), may be exposed in a controlled manner to gastrointestinal fluid. Based on exposure to gastrointestinal fluid, the erodible delay element 904 will erode accordingly, thus providing drug release from the oral drug dosage form 900. The design of the delay component (in FIG. 1K, the delay component comprises the first enteric-based element at pH 902, the second enteric-based element at pH 906, and the erodible delay element 904) may expose certain aspects of the drug component 908 so that a controlled drug release profile of the oral drug dosage form 900 is obtained.

[0090] In some embodiments, the description of the oral drug dosage forms provided in this document, and associated methods, is facilitated by the description of the thickness of a component, such as a layer of an erodible retardant element. In some embodiments, the thickness of a component, such as a layer of an erodible retardant element, is measured from a surface, such as the top surface, in a direction substantially parallel to the erosion direction. For example, as shown in FIG. 1G, the thickness of a layer of an erodible retardant element not mixed with drug 612 is provided.

[0091] An exemplary oral drug dosage form comprising a drug is provided in FIG. 2. As shown in FIG. 2, the oral drug dosage form comprises a non-drug-mixed shell, an internal drug component comprising a first erodible material mixed with a drug and a non-drug-mixed delay component, wherein the delay component comprises two layers of a pH-based enteric element configured to erode at or above a predetermined pH value and three layers of an erodible delay element. Petition 870250088298, dated 09 / 29 / 2025, page 66 / 266 50 / 181 comprising an erodible material, wherein each layer of the pH-based enteric element and the shell prevents erosion of a respective layer of the erodible delay element, and wherein the erodible delay element and the shell prevent erosion of the drug component. After administration, erosion of the pH-based enteric element layers exposes two layers of the erodible delay element to the gastrointestinal fluid such that these two layers of the erodible delay element then begin to erode. Erosion of one of the layers of the erodible delay element exposes a surface of the drug component. Erosion of one of the layers of the erodible delay element exposes another layer of the erodible delay element (described as a VA64 layer, but not limited to such material) on one side of the drug component. After erosion of the VA64 layer of the erodible delay element, another surface of the drug component is exposed.The exposed surfaces of the drug component erode to release the drug from the oral dosage form. As illustrated in FIG. 2, the oral dosage form may contain tracking features, such as tracking bands and / or loops. Such tracking bands are useful for the development and optimization of an oral dosage form, for example, obtaining images of an individual, such as through the use of x-rays, after administration can be used to determine the location of erosion of aspects of the drug dosage form. Oral dosage forms without one or more of the tracking bands are also encompassed by the invention provided in this document. For example, after the development and optimization of the oral dosage form, the tracking bands may no longer be necessary.In these cases, the tracking strip portion can be replaced by the material in which it is incorporated and / or additional adjustments can be made, such as adjusting one or more [sections / parts]. Petition 870250088298, dated 09 / 29 / 2025, page 67 / 266 51 / 181 drug component features (e.g., surface area, thickness, drug mass percentage) to compensate for the absence of the tracking strip. The dimensions indicated in FIG. 2 are provided in Table 1A. Table 1A. Dimensions of an oral drug dosage form illustrated in FIG. 2. Width (mm) Length (mm) Height (mm) Carcass L1 = 8.8 C1 = 12.8 A1 = 4.0 pH-based enteric element layer (both layers have corresponding dimensions) L2 = 8.0 C2 = 12.0 A2 = 0.6 Erodible retardant element layer (both layers have corresponding dimensions) L6 = 7.2 C6 = 11.2 A6 = 0.6 VA64 layer of erodible retardant element L3 = 6.4 C3 = 10.8 A3 = 0.4 Drug component L4 = 1.7 C4 = 9.7 A4 = 1.2 Tracking range L5 = 0.8 C5 = 8.0 A5 = 0.8

[0092] In some embodiments, the shell comprises ethylcellulose (EC, for example, EC-N10), dibutyl sebacate (DBS), and titanium dioxide (T1O2). In some embodiments, the pH-based enteric element comprises vinyl acetate copolymer (VA64), Eudragit® L 100-55 (poly(methacrylic acid-ethyl acrylate; L100-55)), and triethyl citrate (TEC). In some embodiments, the erodible retardant element comprises hydroxypropylcellulose (for example, HPC JF), anhydrous dibasic calcium phosphate (CaHPO4), and TEC. In some embodiments, the erodible retardant element, such as the VA64 layer, comprises VA64 and a polyethylene glycol (PEG, for example, PEG4000). Petition 870250088298, dated 09 / 29 / 2025, pp. 68 / 266 52 / 181 tofacitinib, for example, tofacitinib citrate, barium sulfate (BaSO4) and a PEG, such as PEG20000. In some embodiments, the tracer strip comprises barium sulfate (BaSO4) and a PEG, such as PEG20000.

[0093] In some embodiments, the oral drug dosage form of Table 1A comprises a mass percentage (w / w%) and the total weight of each component as listed in Table 1B. Table 1B. Components of an oral drug dosage form illustrated in FIG. 2. Components Composition (w / w%) Unit (mg per tablet) Eudragit® L 100-55 (poly(methacrylic acid-ethyl coacrylate)) 4.96 20 Vinyl acetate copolymer 19.11 77 Polyethylene glycol 400 0.74 3 Polyethylene glycol 20000 2.47 9.97 Triethyl citrate 7.34 29.6 Hydroxypropylcellulose (Klucel™ JF Farm) 19.06 76.8 Anhydrous dibasic calcium phosphate 2.38 9.6 Tofacitinib citrate 0.52 2.09 Ethylcellulose (Aquaion™ EC-N10 Pharm) 33.75 136 Dibutyl sebacate 5.88 23.68 Titanium dioxide 0.08 0.32 Barium Sulfate 3.71 14.94 Total tablet weight 100 403

[0094] An exemplary oral drug dosage form comprising a drug is provided in FIG. 3. As shown in FIG. 3, the oral drug dosage form comprises a non-containing shell. Petition 870250088298, dated 09 / 29 / 2025, page 69 / 266 53 / 181 mixed with the drug, an internal drug component comprising a first erodible material mixed with a drug, and a delay component not mixed with the drug, wherein the delay component comprises two layers of a pH-based enteric element configured to erode at or above a predetermined pH value and two layers of an erodible delay element comprising an erodible material, wherein each layer of the pH-based enteric element and the casing prevent the erosion of a respective layer of the erodible delay element, and wherein the erodible delay element and the casing prevent the erosion of the drug component. After administration, the erosion of the pH-based enteric element layers then exposes the erodible delay element layers to the gastrointestinal fluid, so that the erodible delay element layers then begin to erode.The erosion of the layers of the erodible retarding element then exposes surfaces of the drug component, so that the erosion of these releases the drug from the oral dosage form. As illustrated in FIG. 3, the oral dosage form may contain tracking bands. Such tracking bands are useful for the development and optimization of an oral dosage form, for example, obtaining images of an individual, such as by using x-rays, after administration can be used to determine the location of erosion of aspects of the drug dosage form. Oral dosage forms without one or more of the tracking bands are also encompassed by the invention provided in this document. For example, after the development and optimization of the oral dosage form, the tracking bands may no longer be necessary. The dimensions indicated in FIG. 3 are provided in Table 2A. Table 2A.Dimensions of an oral medication dosage form illustrated in FIG. 3. Petition 870250088298, dated 09 / 29 / 2025, p. 70 / 266 54 / 181 Width (mm) Length (mm) Height (mm) Carcass L1 = 8.8 C1 = 13.6 A1 = 3.2 pH-based enteric element layer (both layers have corresponding dimensions) L2 = 8.0 C2 = 12.8 A2 = 0.6 Erodible retardant element layer (both layers have corresponding dimensions) L3 = 7.2 C3 = 12.0 A3 = 0.6 Drug component L4 = 4.0 C4 = 8.8 A4 = 0.8 Tracking range L5 = 6.4, L8 = 4.8 C5 = 11.2, C8 = 9.6 A5 = 0.4 Tracking range L6 = 0.8 C6 = 5.6 A6 = 0.4 Tracking range L7 = 8.0, L9 = 7.2 C7 = 12.8, C9 = 12.0 A7 = 0.4

[0095] In some embodiments, the shell comprises ethylcellulose (EC, for example, EC-N10), dibutyl sebacate (DBS), and titanium dioxide (T1O2). In some embodiments, the pH-based enteric element comprises vinyl acetate copolymer (VA64), Eudragit® L 100-55 (poly(methacrylic acid-ethyl acrylate), L100-55), and triethyl citrate (TEC). In some embodiments, the erodible retardant element comprises hydroxypropylcellulose (for example, HPC JF), calcium hydrophosphate (CaHPO4), and TEC. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate, VA64, and TEC. In some embodiments, the tracer band comprises barium sulfate (BaSO4), VA64, and TEC. Petition 870250088298, dated 09 / 29 / 2025, p. 71 / 266 55 / 181

[0096] In some embodiments, the oral drug dosage form of Table 2A comprises a mass percentage (w / w%) and the total weight of each component as listed in Table 2B. Table 2B. Components of an oral drug dosage form illustrated in FIG. 3. Components Composition (w / w%) Unit (mg per tablet) Eudragit® L 100-55 (poly(methacrylic acid ethyl coacrylate)) 5.92 21 Vinyl acetate copolymer 24.34 86.35 Triethyl citrate 10.63 37.72 Hydroxypropylcellulose (Klucel™ JF Farm) 23.45 83.2 Anhydrous dibasic calcium phosphate 2.93 10.4 Tofacitinib citrate 2.50 8.88 Ethylcellulose (Aquaion™ EC-N10 Pharm) 23.11 82 Dibutyl sebacate 5.02 17.8 Titanium dioxide 0.06 0.2 Barium sulfate 2.03 7.2 Total tablet weight 100 354.75

[0097] An exemplary oral drug dosage form comprising a drug is provided in FIG. 4. As shown in FIG. 4, the oral drug dosage form comprises a non-drug-mixed shell, an internal drug component comprising a first erodible material mixed with a drug, and a non-drug-mixed delay component, wherein the delay component comprises two layers of a pH-based enteric element configured to erode at or above a value Petition 870250088298, dated 09 / 29 / 2025, page 72 / 266 56 / 181 of predetermined pH and two layers of an erodible delay element comprising an erodible material, wherein each layer of the pH-based enteric element and the shell prevents erosion of a respective layer of the erodible delay element, and wherein the erodible delay element and the shell prevent erosion of the drug component. After administration, erosion of the pH-based enteric element layers then exposes the erodible delay element layers to gastrointestinal fluid, so that the erodible delay element layers then begin to erode. Erosion of the erodible delay element layers then exposes drug component surfaces, so that erosion of these releases the drug from the oral drug dosage form. As illustrated in FIG. 4, the oral drug dosage form may contain tracking bands.These tracking strips are useful for the development and optimization of an oral drug dosage form, for example, by obtaining images of an individual, such as through the use of x-rays, after administration, which can be used to determine the location of erosion of aspects of the drug dosage form. Oral drug dosage forms without one or more of the tracking strips are also encompassed by the invention provided in this document. For example, after the development and optimization of the oral drug dosage form, the tracking strips may no longer be necessary. The dimensions indicated in FIG. 4 are provided in Table 3A. Table 3A. Dimensions of an oral drug dosage form illustrated in FIG. 4. Width (mm) Length (mm) Thickness (mm) Shell L1 = 8.0 C1 = 12.8 E1 = 3.8 pH-based enteric element layer (both layers have corresponding dimensions) L2 = 5.6 C2 = 10.4 E2 = 0.6 Petition 870250088298, dated 09 / 29 / 2025, p. 73 / 266 57 / 181 Table 3A - continued - Width (mm) Length (mm) Thickness (mm) Erodible retardant element layer (both layers have corresponding dimensions) L3= 4.8 C3= 9.6 E3= 0.8 Drug component L4= 4.0 C4= 8.8 E4= 1.0 Tracking loop L5= 3.2, L5'= 0.4 C5= 8.0 E5= 0.2 Tracking strip L6= 0.8 C6= 5.6 E6= 0.6 Tracking loop L7= 7.2, L7'= 0.4 C7= 12.0 E7= 0.4

[0098] In some embodiments, the shell comprises ethylcellulose (EC, for example, EC-N10), dibutyl sebacate (DBS), and titanium dioxide (T1O2). In some embodiments, the pH-based enteric element comprises vinyl acetate copolymer (VA64), Eudragit® L 100-55 (poly(methacrylic acid-ethyl acrylate); L100-55), triethyl citrate (TEC), and titanium dioxide (T1O2). In some embodiments, the erodible retardant element comprises hydroxypropylcellulose (e.g., HPC JF), TEC, vitamin E succinate polyethylene glycol-1000 (TPGS), and T1O2. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate, VA64, and TEC. In some embodiments, the tracking band or tracking loop comprises barium sulfate (BaSO4), VA64, and TEC.

[0099] In some embodiments, the oral drug dosage form of Table 3A comprises a mass percentage (w / w%) and the total weight of each component as listed in Table 3B. Petition 870250088298, dated 09 / 29 / 2025, page 74 / 266 58 / 181 Table 3B. Components of an oral drug dosage form illustrated in FIG. 4. Components Composition (w / w%) Unit (mg per tablet) Eudragit® L 100-55 (poly(methacrylic acid-ethyl acrylate)) 3.47 12.8 Vitamin E succinate polyethylene glycol 1000 (TPGS) 1.00 3.70 Vinyl acetate copolymer 16.79 62.01 Triethyl citrate 8.20 30.27 Hydroxypropylcellulose (Klucel™ JF Farm) 15.97 58.97 Tofacitinib citrate 2.40 8.88 Ethylcellulose (Aquaion™ EC-N10 Pharm) 41.08 151.73 Dibutyl sebacate 8.92 32.93 Titanium dioxide 0.18 0.65 Barium sulfate 2.01 7.42 Total weight of 100 tablets 369.36

[0100] An exemplary oral drug dosage form comprising a drug is provided in FIG. 4. As shown in FIG. 4, the oral drug dosage form comprises a shell not mixed with the drug, an internal drug component comprising a first erodible material mixed with a drug, and a retarding component not mixed with the drug, wherein the retarding component comprises two layers of a pH-based enteric element configured to erode at or above a predetermined pH value and two layers of an erodible retarding element comprising an erodible material, wherein each layer of the pH-based enteric element and the shell prevents erosion of a Petition 870250088298, dated 09 / 29 / 2025, page 75 / 266 59 / 181 respective layer of the erodible delay element, wherein the erodible delay element and the shell prevent erosion of the drug component. After administration, erosion of the pH-based enteric element layers then exposes the erodible delay element layers to gastrointestinal fluid, so that the erodible delay element layers then begin to erode. Erosion of the erodible delay element layers then exposes drug component surfaces, so that erosion of these releases the drug from the oral dosage form. As illustrated in FIG. 4, the oral dosage form may contain tracking bands.These tracking strips are useful for the development and optimization of an oral drug dosage form, for example, obtaining images of an individual, such as through the use of x-rays, after administration can be used to determine the location of erosion of aspects of the drug dosage form. Oral drug dosage forms without one or more of the tracking strips are also encompassed by the invention provided in this document. For example, after the development and optimization of the oral drug dosage form, the tracking strips may no longer be necessary. The dimensions indicated in FIG. 4 are provided in Table 4A. Table 4A. Dimensions of an oral drug dosage form illustrated in FIG. 4. Width (mm) Length (mm) Thickness (mm) Shell L1 = 8.0 C1 = 12.8 E1 = 3.83 pH-based enteric element layer (both layers have corresponding dimensions) L2 = 5.6 C2 = 10.4 E2 = 0.6 Erodible retardant element layer (both layers have corresponding dimensions) L3 = 4.8 C3 = 9.6 E3 = 0.84 Petition 870250088298, dated 09 / 29 / 2025, p. 76 / 266 60 / 181 Table 4A. -continued- Width (mm) Length (mm) Thickness (mm) Drug component L4= 4.0 C4= 8.8 E4= 0.95 Tracking loop L5= 3.2, L5'= 0.4 C5= 8.0 E5= 0.19 Tracking range L6= 0.8 C6= 5.6 E6= 0.57 Tracking loop L7= 7.2, L7'= 0.4 C7= 12.0 E7= 0.42

[0101] In some embodiments, the shell comprises ethylcellulose (EC, for example, EC-N10), dibutyl sebacate (DBS), and titanium dioxide (T1O2). In some embodiments, the pH-based enteric element comprises vinyl acetate copolymer (VA64), Eudragit® L 100-55 (poly(methacrylic acid-ethyl acrylate); L100-55), triethyl citrate (TEC), and titanium dioxide (T1O2). In some embodiments, the erodible retardant element comprises hydroxypropylcellulose (e.g., HPC JF), TEC, vitamin E succinate polyethylene glycol-1000 (TPGS), and T1O2. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate, VA64, and TEC. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the tracking band or tracking loop comprises barium sulfate (BaSO4), VA64, and TEC.

[0102] In some embodiments, the oral drug dosage form of Table 4A comprises a mass percentage (w / w%) and the total weight of each component as listed in Table 4B. Table 4B. Components of an oral drug dosage form illustrated in FIG. 4. Petition 870250088298, dated 09 / 29 / 2025, page 77 / 266 61 / 181 Components Composition (w / w%) Unit (mg per tablet) Eudragit® L 100-55 (poly(methacrylic acid-ethyl acrylate)) 3.42 12.8 Vitamin E succinate polyethylene glycol 1000 (TPGS) 1.04 3.88 Vinyl acetate copolymer 15.73 58.90 Triethyl citrate 8.04 30.08 Hydroxypropylcellulose (Klucel™ JF Farm) 16.54 61.92 Tofacitinib citrate 2.37 8.88 Ethylcellulose (Aquaion™ EC-N10 Pharm) 40.85 152.93 Dibutyl sebacate 8.87 33.20 Titanium dioxide 0.18 0.66 Barium sulfate 2.97 11.10 Total weight of tablet 100 374.35

[0103] An exemplary oral drug dosage form comprising a drug is described below based on the dimensional descriptors provided in FIG. 11. The oral drug dosage form of FIG. 11 does not comprise a shell. As shown in FIG. 11, the oral drug dosage form comprises an internal drug component comprising a first erodible material mixed with a drug, and a delay component not mixed with the drug, wherein the delay component comprises a pH-based enteric element configured to erode at or above a predetermined pH value and an erodible delay element comprising an erodible material. After administration, erosion of the pH-based enteric element then exposes at least a portion of the erodible delay element to gastrointestinal fluid, such that the erodible delay element (or portions thereof) then begins to erode. Petition 870250088298, dated 09 / 29 / 2025, page 78 / 266 62 / 181 The erosion of the erodible retarding element then exposes one or more surfaces of the drug component, such that the erosion of this component releases the drug from the oral dosage form. As illustrated in FIG. 11, the oral dosage form may contain a tracking feature, such as a tracking band or loop (these terms may be used interchangeably). Such tracking bands are useful for the development and optimization of an oral dosage form, for example, by obtaining images of an individual, such as by using x-rays, after administration can be used to determine the location of erosion of aspects of the drug dosage form. Oral dosage forms without one or more of the tracking bands are also encompassed by the invention provided herein.For example, after the development and optimization of the oral drug dosage form, the tracking bands may no longer be necessary. The dimensions indicated in FIG. 11 are provided in Table 5A. A1 is 2.38 mm and A2 is 1.92 mm. Table 5A. Dimensions of an oral drug dosage form illustrated in FIG. 11. Width (mm) Length (mm) Thickness (mm) PH-based enteric element L1 = 7.6 C1 = 15.0 E1 = 4.3 Erodible retardant element L2 = 6.8 C2 = 14.2 E2 = 4.0 Drug component L3 = 3.2 C3 = 10.6 E3 = 0.92 Tracking loop L4 = 3.2, L4' = 0.4 C4 = 10.6 E4 = 0.23 Tracking band L5 = 0.8 C5 = 8.2 E5 = 0.46

[0104] In some embodiments, the pH-based enteric element comprises hypromellose acetate succinate AS-LG (HPMCAS LG), triethyl citrate (TEC), and titanium dioxide (T1O2). In some embodiments, the erodible retardant element comprises hydroxypropylcellulose. Petition 870250088298, dated 09 / 29 / 2025, page 79 / 266 63 / 181 (e.g., HPC JF), TEC, vitamin E succinate, polyethylene glycol 1000 (TPGS), and T1O2. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate, VA64, and TEC. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the tracking band or tracking loop comprises barium sulfate (BaSO4), VA64, and TEC.

[0105] In some embodiments, the oral drug dosage form of Table 5A comprises a mass percentage (w / w%) and the total weight of each component as listed in Table 5B. Table 5B. Components of an oral drug dosage form illustrated in FIG. 11. Components Composition (w / w%) Unit (mg per tablet) Hypromellose Acetate Succinate AS-LG 17.13 87.78 Vitamin E Succinate Polyethylene Glycol 1000 (TPGS) 3.55 18.20 Vinyl Acetate Copolymer 3.54 18.12 Triethyl Citrate 15.93 81.61 Hydroxypropylcellulose (Klucel™ JF Farm) 56.69 290.47 Tofacitinib Citrate 1.73 8.88 Titanium Dioxide 0.19 0.95 Barium Sulfate 1.25 6.40 Total tablet weight 100 512.41 Petition 870250088298, dated 09 / 29 / 2025, page 80 / 266 64 / 181

[0106] An exemplary oral drug dosage form comprising a drug is described below based on the dimensional descriptors provided in FIG. 11. The oral drug dosage form of FIG. 11 does not comprise a shell. As illustrated in FIG. 11, the oral drug dosage form may contain a tracking feature, such as a tracking band or loop (such terms may be used interchangeably). Such tracking bands are useful for the development and optimization of an oral drug dosage form, for example, obtaining images of an individual, such as by means of the use of x-rays, after administration can be used to determine the location of erosion of aspects of the drug dosage form. Oral drug dosage forms without one or more of the tracking bands are also encompassed by the invention provided in this document.For example, after the development and optimization of the oral drug dosage form, the tracking bands may no longer be necessary. The dimensions indicated in FIG. 11 are provided in Table 6A. A1 is 1.59 mm and A2 is 1.13 mm. Table 6A. Dimensions of an oral drug dosage form illustrated in FIG. 11. Width (mm) Length (mm) Thickness (mm) pH-based enteric element L1 = 7.6 C1 = 15.0 E1 = 2.72 Erodible retardant element L2 = 6.8 C2 = 14.2 E2 = 2.42 Drug component L3 = 3.2 C3 = 10.6 E3 = 0.92 Tracking loop L4 = 3.2, L4' = 0.4 C4 = 10.6 E4 = 0.23 Tracking band L5 = 0.8 C5 = 8.2 E5 = 0.46

[0107] In some embodiments, the pH-based enteric element comprises hypromellose acetate succinate AS-LG (HPMCAS LG), Petition 870250088298, dated 09 / 29 / 2025, p. 81 / 266 65 / 181 triethyl citrate (TEC) and titanium dioxide (T1O2). In some embodiments, the erodible retardant element comprises hydroxypropylcellulose (e.g., HPC JF), TEC, vitamin E succinate, polyethylene glycol-1000 (TPGS), and T1O2. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate, VA64, and TEC. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the tracking band or tracking loop comprises barium sulfate (BaSO4), VA64, and TEC.

[0108] In some embodiments, the oral drug dosage form of Table 6A comprises a mass percentage (w / w%) and the total weight of each component as listed in Table 6B. Table 6B. Components of an oral drug dosage form illustrated in FIG. 11. Components Composition (w / w%) Unit (mg per tablet) Hypromellose Acetate Succinate ASLG 21.74 71.82 Vitamin E Succinate Polyethylene Glycol-1000 (TPGS) 3.06 10.10 Vinyl Acetate Copolymer 5.48 18.12 Triethyl Citrate 16.13 53.31 Hydroxypropylcellulose (Klucel™ JF Farm) 48.79 161.20 Tofacitinib Citrate 2.69 8.88 Titanium Dioxide 0.18 0.58 Barium Sulfate 1.94 6.40 Total tablet weight 100 330.41 Petition 870250088298, dated 09 / 29 / 2025, page 82 / 266 66 / 181

[0109] An exemplary oral drug dosage form comprising a drug is described below based on the dimensional descriptors provided in FIG. 11. The oral drug dosage form of FIG. 11 does not comprise a shell. As illustrated in FIG. 11, the oral drug dosage form may contain a tracking feature, such as a tracking band or loop (such terms may be used interchangeably). Such tracking bands are useful for the development and optimization of an oral drug dosage form, for example, obtaining images of an individual, such as by means of the use of x-rays, after administration can be used to determine the location of erosion of aspects of the drug dosage form. Oral drug dosage forms without one or more of the tracking bands are also encompassed by the invention provided in this document.For example, after the development and optimization of the oral drug dosage form, the tracking strips may no longer be necessary. The dimensions indicated in FIG. 11 are provided in Table 7A. Table 7A. Dimensions of an oral drug dosage form illustrated in FIG. 11. Width (mm) Length (mm) Thickness (mm) PH-based enteric element L1 = 7.6 C1 = 15.0 E1 = 3.02 Erodible retardant element L2 = 6.8 C2 = 14.2 E2 = 2.72 Drug component L3 = 3.2 C3 = 10.6 E3 = 0.92 Tracking loop L4 = 3.2, L4' = 0.4 C4 = 10.6 E4 = 0.23 Tracking band L5 = 0.8 C5 = 8.2 E5 = 0.46

[0110] In some embodiments, the pH-based enteric element comprises hypromellose acetate succinate AS-LG (HPMCAS LG), triethyl citrate (TEC), and titanium dioxide (T1O2). In some embodiments, the erodible retardant element comprises hydroxypropylcellulose. Petition 870250088298, dated 09 / 29 / 2025, page 83 / 266 67 / 181 (e.g., HPC JF), TEC, vitamin E succinate, polyethylene glycol 1000 (TPGS), and T1O2. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate, VA64, and TEC. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the tracking band or tracking loop comprises barium sulfate (BaSO4), VA64, and TEC.

[0111] In some embodiments, the oral drug dosage form of Table 7A comprises a mass percentage (w / w%) and the total weight of each component as listed in Table 7B. Table 7B. Components of an oral drug dosage form illustrated in FIG. 11. Components Composition (w / w%) Unit (mg per tablet) Hypromellose Acetate Succinate ASLG 20.57 75.56 Vitamin E Succinate Polyethylene Glycol 1000 (TPGS) 3.19 11.72 Vinyl Acetate Copolymer 4.93 18.12 Triethyl Citrate 16.05 58.97 Hydroxypropylcellulose (Klucel™ JF Farm) 50.92 187.05 Tofacitinib Citrate 2.42 8.88 Titanium Dioxide 0.18 0.65 Barium Sulfate 1.74 6.40 Total tablet weight 100 367.35 Petition 870250088298, dated 09 / 29 / 2025, page 84 / 266 68 / 181

[0112] An exemplary oral drug dosage form comprising one drug is described below based on the dimensional descriptors provided in FIG. 11. The oral drug dosage form of FIG. 11 does not include a shell or tracking bands. The dimensions indicated in FIG. 11 are provided in Table 8A. Table 8A. Dimensions of an oral drug dosage form illustrated in FIG. 11. Width (mm) Length (mm) Thickness (mm) pH-based enteric element L1 = 7.6 C1 = 17.0 E1 = 5.15 Erodible retardant element L2 = 6.8 C2 = 16.2 E2 = 4.75 Drug component L3 = 2.6 C3 = 12 E3 = 1.25

[0113] In some embodiments, the pH-based enteric element comprises hypromellose acetate succinate AS-LG (HPMCAS LG), acetyltributyl citrate (ATBC), and titanium dioxide (T1O2). In some embodiments, the erodible retardant element comprises hydroxypropylcellulose (e.g., HPC JF), TEC, vitamin E succinate polyethylene glycol-1000 (TPGS), and T1O2. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate. In some embodiments, the drug component comprises a drug, such as tofacitinib, for example, tofacitinib citrate, VA64, hydroxypropylcellulose (HPC SSL), and triacetin.

[0114] In some embodiments, the oral drug dosage form of Table 8A comprises a mass percentage (w / w%) and the total weight of each component as listed in Table 8B. Table 8B. Components of an oral drug dosage form illustrated in FIG. 11. Petition 870250088298, dated 09 / 29 / 2025, page 85 / 266 69 / 181 Components Composition (w / w%) Unit (mg per tablet) Hypromellose Acetate Succinate AS-LG 18.84 135.12 Tributyl Citrate (ATBC) 6.30 45.16 Vitamin E Succinate Polyethylene Glycol-1000 (TPGS) 3.43 24.64 Vinyl Acetate Copolymer 2.29 16.43 Triethyl Citrate 10.30 73.92 Hydroxypropylcellulose (Klucel™ JF Farm) 54.82 393.28 Tofacitinib Citrate 1.24 8.88 Titanium Dioxide 0.11 0.82 Hydroxypropylcellulose (HPC SSL) 1.55 11.1 Triacetin 1.11 7.99 Total tablet weight 100 717.34 B. Components and configurations of oral drug dosage forms described in this document

[0115] In certain respects, an oral drug dosage form comprising the following components is provided in this document: (1) a drug component comprising an erodible material mixed with a drug; and (2) a retardation component not mixed with the drug, wherein the retardation component comprises a pH-based enteric element configured to erode at or above a predetermined pH value; and optionally, any one or more additional features described in this document, for example, (i) an erodible retardation element comprising an erodible material; (ii) a bacterial degradation element comprising a bacterial degradation moiety; or (iii) a component Petition 870250088298, dated 09 / 29 / 2025, page 86 / 266 70 / 181 of excipient comprising an excipient. In any of the above embodiments, the oral drug dosage form may comprise a shell not mixed with the drug. The components described in this document may be in the form of one or more layers. In some embodiments, the delay component of the oral drug dosage form comprises more than one set of layers of a pH-based enteric element and, optionally, an erodible delay element (for example, a first set of a first layer of a pH-based enteric element and a first layer of an erodible delay element, and a second set of a second layer of a pH-based enteric element and a second layer of an erodible delay element).Furthermore, the components of an oral drug dosage form described in this document may be arranged such that the oral drug dosage form comprises one or more compartments, for example, a first compartment comprising a drug component and a second compartment comprising a bacterial degradation element and / or an excipient.

[0116] In some embodiments, an oral drug dosage form is provided that is configured to release a drug at a desired location in an individual’s colon, the oral drug dosage form comprising: a drug component comprising an erodible material mixed with the drug; and a delay component not mixed with the drug, wherein the delay component is configured to prevent the release of the drug from the drug component until the oral drug dosage form reaches the individual’s colon after administration, and wherein the delay component comprises: a pH-based enteric element comprising an erodible material configured to erode at or above a predetermined pH value. Petition 870250088298, dated 09 / 29 / 2025, page 87 / 266 71 / 181

[0117] In some embodiments, the oral drug dosage form does not comprise an erodible retardant element; for example, the oral drug dosage form consists essentially of the drug component and the pH-based enteric element. In some embodiments, the erodible material of the pH-based enteric element comprises one or more of hypromellose acetate succinate, hydroxypropylmethylcellulose phthalate, cellulose acetate propionate (CAP), poly(ethyl methacrylic acid-co-acrylate), or polyvinyl acetate phthalate (PVAP). In some embodiments, the hypromellose acetate succinate is HPMCAS LG / LF, HPMCAS MG / MF, or HPMCAS HG / LF. In some embodiments, the hydroxypropylmethylcellulose phthalate is HPMCP HP-50 or HPMCP HP-55. In some embodiments, poly(ethyl methacrylic acid-co-acrylate) is Eudragit L100-55 or Eudragit L100.

[0118] In some embodiments, an oral drug dosage form is provided that is configured to release a drug at a desired location in an individual's colon, the oral drug dosage form comprising: a drug component comprising an erodible material mixed with the drug; and a delay component not mixed with the drug, wherein the delay component is configured to prevent the release of the drug from the drug component until the oral drug dosage form reaches the individual's colon after administration, and wherein the delay component comprises: a pH-based enteric element comprising an erodible material configured to erode at or above a predetermined pH value, and an erodible delay element, and wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible delay element.In some formulations, the oral drug dosage form is configured so that the enteric-based pH element erodes. Petition 870250088298, dated 09 / 29 / 2025, p. 88 / 266 72 / 181 before the erodible retarding element. In these embodiments, it is not necessary for the pH-based enteric element to erode completely before the erosion of the erodible retarding element begins (although, in some embodiments, this occurs). In some embodiments, the pH-based enteric element at least partially prevents the erosion of the erodible retarding element (such as directly, for example, the pH-based enteric element is in contact with the erodible retarding element), and the erodible retarding element at least partially prevents the erosion of the drug component (such as directly, for example, the erodible retarding element is in contact with the drug component). In some embodiments, the oral drug dosage form comprises one or more intermediate materials positioned between other components of an oral drug dosage form, such as an intermediate material not mixed with the drug.

[0119] In the embodiments provided in this document, the oral drug dosage form comprises a second drug. The second drug may be positioned in and / or mixed with any aspect of the oral drug dosage form. In some embodiments, the second drug is mixed into the drug component. In some embodiments, the oral drug dosage form further comprises a second drug component mixed with the second drug (which may be the same as or different from the drug of the drug component). The second drug component mixed with the second drug component may be positioned in a variety of configurations based on the desired release of the second drug and, in some embodiments, of the drug. For example, in some embodiments, the drug component is incorporated into the second drug component, wherein the oral drug dosage form is configured so that the enteric element to Petition 870250088298, dated 09 / 29 / 2025, p. 89 / 266 73 / 181 pH base erodes before the erodible delay element, the erodible delay element erodes before the second drug component, the second drug component erodes before the second erodible delay element, and the second erodible delay element erodes before the drug component. In some embodiments, the second drug component is located in a compartment separate from the drug component, for example, allowing independent release of the second drug and the drug. In some embodiments, the oral drug dosage form comprises a second drug component and a second erodible delay component.In this embodiment, the oral drug dosage form is configured so that the pH-based enteric element erodes before the erodible delay element, the erodible delay element erodes before the second drug component, the second drug component erodes before the second erodible delay element, and the second erodible delay element erodes before the drug component. The above embodiments may be extended to include additional drugs and drug components, such as two or more drugs, three or more drugs, four or more drugs, and five or more drugs.

[0120] In the embodiments provided in this document, the oral drug dosage form comprises a bacterial degradation portion. The bacterial degradation portion may be positioned in and / or mixed with aspects of the oral drug dosage form; however, generally the bacterial degradation portion will not be mixed with the pH-based enteric element. In some embodiments, the bacterial degradation portion is mixed with the erodible material of the erodible retardant element. In some embodiments, the bacterial degradation portion is mixed with the component of Petition 870250088298, dated 09 / 29 / 2025, page 90 / 266 74 / 181 drug. For example, in some embodiments, the drug component provides controlled release of a drug in the colon, wherein the drug component additionally comprises a bacterial degradation moiety. In some embodiments, the oral drug dosage form comprises a bacterial degradation element comprising an erodible material mixed with the bacterial degradation moiety. The bacterial degradation element may be positioned in a variety of configurations.For example, in some embodiments, the retarding component further comprises a bacterial degradation element comprising an erodible material mixed with the bacterial degradation portion, wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible retarding element, the erodible retarding element erodes before the bacterial degradation element, and the bacterial degradation element erodes before the drug component. In some embodiments, the pH-based enteric element at least partially prevents erosion of the erodible retarding element, the erodible retarding element at least partially prevents erosion of the bacterial degradation element, and the bacterial degradation element at least partially prevents erosion of the drug component.In some embodiments, the bacterial degradation portion and / or the bacterial degradation element are located in a compartment separate from the drug component.

[0121] In the embodiments provided in this document, the oral drug dosage form comprises an excipient. The excipient may be positioned in and / or mixed with any aspects of the oral drug dosage form. In some embodiments, the excipient is mixed with the erodible material of the erodible retardant element. In some embodiments, the excipient is mixed with the component of Petition 870250088298, dated 09 / 29 / 2025, page 91 / 266 75 / 181 drug. In some embodiments, the oral drug dosage form comprises an excipient component comprising an erodible material mixed with an excipient. The excipient component may be positioned in a variety of configurations. For example, in some embodiments, the excipient component further comprises an erodible material mixed with an excipient, wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before an erodible retarding element, the erodible retarding element erods before the excipient component, and the excipient component erods before the drug component. In some embodiments, the excipient and / or excipient component are located in a compartment separate from the drug component.

[0122] In some embodiments, the excipient is an absorption enhancer. In some embodiments, the oral drug dosage form is configured for local release, wherein the oral drug dosage form does not comprise an excipient that is an absorption enhancer. In some embodiments, the oral drug dosage form is configured for systemic release, wherein the oral drug dosage form comprises an excipient that is an absorption enhancer.

[0123] In the embodiments provided in this document, the oral drug dosage form comprises an adjuvant. The adjuvant may be positioned in and / or mixed with any aspects of the oral drug dosage form. In some embodiments, the adjuvant is mixed with the erodible material of the erodible delay element. In some embodiments, the adjuvant is mixed with the drug component. In some embodiments, the oral drug dosage form comprises an adjuvant component comprising an erodible material mixed with an adjuvant. The adjuvant component Petition 870250088298, dated 09 / 29 / 2025, p. 92 / 266 76 / 181 can be positioned in a variety of configurations. For example, in some embodiments, the excipient component further comprises an erodible material mixed with an adjuvant, wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before an erodible retarding element, the erodible retarding element erodes before the adjuvant component, and the adjuvant component erodes before the drug component. In some embodiments, the adjuvant and / or the adjuvant component are located in a compartment separate from the drug component. In some embodiments, the adjuvant is selected based on whether the drug is a biological drug. For example, in some embodiments, when the drug is a peptide biological drug, the adjuvant is a protease scavenger and / or a protease inhibitor.In some embodiments, when the drug is a nucleic acid biologic, the adjuvant is a lipid nanoparticle (LNP). In some embodiments, the lipid nanoparticle is selected from the group consisting of ionizable lipids, auxiliary lipids, cholesterol, and pegylated lipids (PEG-lipids).

[0124] In some embodiments, the oral drug dosage form does not comprise a shell. In some embodiments, the oral drug dosage form comprises a shell not mixed with a drug of a drug component. In these embodiments, the oral drug dosage form is configured so that the shell, or a part thereof, and the delay element prevent erosion of the drug component. In some embodiments, the direction of erosion of the delay component and / or the drug component is based on the configuration of the shell.

[0125] For any of the oral drug dosage forms described in this document, one or more aspects of the oral drug dosage form may be configured in the form of a layer, such as Petition 870250088298, dated 09 / 29 / 2025, p. 93 / 266 77 / 181 as a layer with an upper surface, a lower surface, and a thickness. Furthermore, geometric configurations of aspects of oral drug dosage forms are provided for in this document, such as a drug component comprising a spherical shape, or a part thereof. In some embodiments, one or more aspects of the oral drug dosage form may be configured in the form of a compartment. In some embodiments, the oral drug dosage form comprises one or more compartments comprising one or more drug components. In some embodiments, the oral drug dosage form comprises one or more compartments comprising one or more drug components and one or more additional aspects, such as an excipient and / or adjuvant component.

[0126] The oral drug dosage forms described in this document may, for example, have any size, shape, or weight suitable for oral administration. In some embodiments, the oral drug dosage form is suitable for oral administration to an individual where the size, shape, and / or weight of the oral drug dosage form is based on an attribute of the individual. In some embodiments, an attribute of an individual is one or more of height, weight, or age. In some embodiments, the individual is an infant. In some embodiments, the individual is a child. In some embodiments, the individual is an adolescent. In some embodiments, the individual is an adult.

[0127] In some embodiments, the largest dimension traversing an oral drug dosage form, for example, the largest diameter, is from about 1 mm to about 25 mm, as is any of about 2 mm to about 10 mm, about 5 mm to about 12 mm, about 8 mm to about 15 mm, about 5 mm to about 10 mm, or about 7 mm to about 9 mm. In some embodiments, the largest Petition 870250088298, dated 09 / 29 / 2025, p. 94 / 266 78 / 181 dimension that traverses an oral drug dosage form, for example, the largest diameter, is less than about 25 mm, such as less than about any of 24 mm, 23 mm, 22 mm, 21 mm, 20 mm, 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, 2 mm or 1 mm. In some embodiments, the largest dimension that traverses an oral drug dosage form, for example, the largest diameter, is greater than about 1 mm, such as greater than about any of 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, or 25 mm.In some embodiments, the largest dimension that passes through an oral drug dosage form, for example, the largest diameter, is approximately any one of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, or 25 mm.

[0128] In some embodiments, the oral drug dosage form has a thickness of about 1 mm to about 25 mm, such as any of about 2 mm to about 10 mm, about 5 mm to about 12 mm, about 8 mm to about 15 mm, about 5 mm to about 10 mm or about 7 mm to about 9 mm. In some embodiments, the oral drug dosage form has a thickness less than about 25 mm, such as less than about any of 24 mm, 23 mm, 22 mm, 21 mm, 20 mm, 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, 2 mm, or 1 mm. In some embodiments, the oral drug dosage form has a thickness greater than about 1 mm, such as greater than about any of 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, Petition 870250088298, dated 09 / 29 / 2025, p. 95 / 266 79 / 181 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, or 25 mm. In some embodiments, the oral drug dosage form has a thickness of approximately any one of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm, or 25 mm.

[0129] In some embodiments, the shape of an oral drug dosage form comprises a cylinder, oval, projectile shape, arrowhead shape, triangle, arched triangle, square, arched square, rectangle, arched rectangle, rhombus, pentagon, hexagon, octagon, half-moon, almond or a combination thereof.

[0130] In some embodiments, the shape of an oral drug dosage form comprises a cylinder, oval, projectile shape, arrowhead shape, triangle, arched triangle, square, arched square, rectangle, arched rectangle, rhombus, pentagon, hexagon, octagon, half-moon, almond, or a combination thereof, wherein the largest dimension traversing the oral drug dosage form, for example, the largest diameter, is about any one of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, 21 mm, 22 mm, 23 mm, 24 mm or 25 mm.

[0131] In some embodiments, the total weight of an oral drug dosage form is from about 20 mg to about 1500 mg, such as about any of about 50 mg to about 150 mg, about 150 mg to about 250 mg, about 160 mg to about 170 mg, about 250 mg to about 350 mg, about 350 mg to about 450 mg, about 450 mg to about 550 mg, about 550 mg to about 650 mg, about 650 mg to about 750 mg, about 750 mg Petition 870250088298, dated 09 / 29 / 2025, page 96 / 266 80 / 181 to about 850 mg, about 850 mg to about 950 mg, about 950 mg to about 1050 mg, about 1050 mg to about 1150 mg, about 1150 mg to about 1250 mg, about 1250 mg to about 1350 mg or approximately 1350 mg to approximately 1450 mg. In some embodiments, the total weight of an oral drug dosage form is less than about 1500 mg, such as less than about any of the following: 1450 mg, 1400 mg, 1350 mg, 1300 mg, 1250 mg, 1200 mg, 1150 mg, 1100 mg, 1050 mg, 1000 mg, 950 mg, 900 mg, 850 mg, 800 mg, 750 mg, 700 mg, 650 mg, 600 mg, 550 mg, 500 mg, 475 mg, 450 mg, 425 mg, 400 mg, 375 mg, 350 mg, 325 mg, 300 mg, 275 mg, 250 mg, 225 mg, 200 mg. 175 mg, 150 mg, 125 mg, 100 mg, 95 mg, 90 mg, 85 mg, 80 mg, 75 mg, 70 mg, 65 mg, 60 mg, 55 mg, 50 mg, 45 mg, 40 mg, 35 mg, 30 mg or 25 mg.In some embodiments, the total weight of an oral drug dosage form is greater than about 20 mg, such as greater than about any of 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 125 mg, 150 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg, 1150 mg, 1200 mg, 1250 mg, 1300 mg, 1350 mg, 1400 mg, or 1450 mg. In some embodiments, the total weight of an oral drug dosage form is approximately any one of 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 125 mg, 150 mg, 160 mg. 165 mg, 170 mg, 175 mg, 200 mg, 225 mg, 250 mg, 275 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg, 1150 mg, 1200 mg, 1250 mg, 1300 mg, 1350 mg, 1400 mg or 1450 mg. Petition 870250088298, dated 09 / 29 / 2025, page 97 / 266 81 / 181

[0132] As described in this document, the components of oral drug dosage forms can be configured in various shapes and sizes. Unless otherwise specified, reference to specific shapes, sizes, and measurements reflects the oral drug dosage form prior to administration to a human subject, for example, prior to erosion of any of its components. A more detailed discussion of the components of the oral drug dosage forms provided in this document is included in the sections below. The modular discussion of these components does not limit the scope of the invention, and a person skilled in the art will readily understand how certain features of the sections below can be combined for the oral drug dosage forms taught in this document. 1. Drug components

[0133] The oral drug dosage forms described in this document comprise a drug component comprising an erodible material mixed with a drug. The drug components encompassed in this document may be formed using various materials (including materials with a variety of drug mass fractions) with varying shapes, sizes, and erosion rates. In some embodiments, the oral drug dosage form comprises a second drug component comprising a drug, wherein the drug and / or the erodible material of the drug component and the second drug component may be the same or different. In some embodiments, the oral drug dosage form comprises more than one compartment, and various drug component configurations are provided herein, such that one compartment may contain one drug component, more than one with Petition 870250088298, dated 09 / 29 / 2025, page 98 / 266 82 / 181 drug component or no drug component. Additional drug component description applies to additional drug components, such as a second drug component.

[0134] In some embodiments, the drug component is a layer. In some embodiments, the drug component comprises a plurality of spheres, such as a layer comprising a plurality of nanoparticles.

[0135] In some embodiments, the drug component is surrounded, such as completely surrounded, by a delay component (e.g., a pH-based enteric element and, optionally, an erodible delay element and / or a shell). In some embodiments, the drug component is configured to have surfaces, including one or more surfaces designed to be exposed to a body fluid (e.g., a gastrointestinal fluid) after administration of the oral drug dosage form to a human subject and after erosion / dissolution of a delay component. In some embodiments, the drug component is a layer comprising an upper surface and a lower surface. In some embodiments, the drug component comprises one or more sides, such as a side substantially perpendicular to an upper surface or a lower surface of a drug component.In some embodiments, at least one of the sides of the drug components is associated with (such as in direct contact with) an aspect of the delay component and / or an oral drug dosage form shell. For example, in some embodiments, the oral drug dosage form is configured such that, after erosion of a delay component comprising a pH-based enteric element and, optionally, an erodible delay element, the drug component maintains its position relative to the shell for a period of time, while at least one... Petition 870250088298, dated 09 / 29 / 2025, page 99 / 266 83 / 181 part of the drug component erodes in the presence of a body fluid.

[0136] In some embodiments, the drug component has a predetermined shape and / or surface area, such as configured to provide a desired drug release profile from an oral drug dosage form. For example, in some embodiments, the drug component releases a drug from an oral drug dosage form based on erosion of the drug component at any interface exposed to a body fluid (such as an upper surface and / or a lower surface). In some embodiments, the drug component has an upper surface and a lower surface, such as those delimited by exposure to a body fluid during administration to an individual. In some embodiments, the upper and lower surfaces of the drug component are exposed to a body fluid simultaneously.In some embodiments, the upper and / or lower surface of the drug component, or at least a portion thereof, is flat (such as within a surface tolerance limit measured between two parallel planes). In some embodiments, the upper and / or lower surface of the drug component is not flat, for example, it comprises certain features that extend beyond an upper surface plane or a surface tolerance limit. The surface(s) of the drug component exposed to a body fluid, such as an upper and / or lower surface, based on the surface exposed to the body fluid, may have any shape. In some embodiments, the surface(s) of the drug component exposed to a body fluid has the shape of a capsule, circle, oval, projectile shape, arrowhead shape, triangle, or triangle. Petition 870250088298, dated 09 / 29 / 2025, pp. 100 / 266 84 / 181 arched, square, arched square, rectangle, arched rectangle, rhombus, pentagon, hexagon, octagon, half-moon, almond or a combination thereof.

[0137] In some embodiments, the surface(s) of a drug component initially exposed to a body fluid, such as an upper surface and a lower surface, have a surface area of ​​about 10 mm2 to about 400 mm2, such as any of about 20 mm2 to about 200 mm2, about 20 mm2 to about 100 mm2, about 20 mm2 to about 60 mm2, about 30 mm2 to about 50 mm2.In some embodiments, the surface(s) of a drug component initially exposed to a body fluid, such as an upper surface and a lower surface, have a surface area of ​​at least about 20 mm², such as at least about any of 22 mm², 24 mm², 28 mm², 30 mm², 32 mm², 33 mm², 34 mm², 36 mm², 38 mm², 42 mm², 44 mm², 46 mm², 48 mm², 50 mm², 52 mm², 54 mm², 58 mm², 60 mm², 65 mm², 70 mm², 80 mm², 85 mm², 90 mm², 100 mm², 110 mm², 120 mm², 130 mm², 140 mm2, 150 mm2, 160 mm2, 170 mm2, 180 mm2, 190 mm2, 200 mm2, 225 mm2, 250 mm2, 275 mm2, 300 mm2, 325 mm2, 350 mm2, 375 mm2or 400 mm2.In some embodiments, the surface(s) of a drug component initially exposed to a body fluid, such as an upper surface and a lower surface, have a surface area less than about 400 mm², such as less than about any of 400 mm², 375 mm², 350 mm², 325 mm², 300 mm², 275 mm², 250 mm², 225 mm², 200 mm², 190 mm², 180 mm², 170 mm², 160 mm², 150 mm², 140 mm², 130 mm², 120 mm², 110 mm², 100 mm², 95 mm², 90 mm², 85 mm², 80 mm², 75 mm², 70 mm², 65 mm², 60 mm2, 58 mm2, 56 mm2, 54 mm2, 52 mm2, 50 mm2, 48 mm2, 46 mm2, 44 mm2, 42 mm2, 40 mm2, 38 mm2, 36 mm2, 34 mm2, 32 mm2, 30 mm2, 28 mm2,. Petition 870250088298, dated 09 / 29 / 2025, pp. 101 / 266 85 / 181 mm2, 24 mm2, 22 mm2 or 20 mm2. In some embodiments, the surface(s) of a drug component initially exposed to a body fluid, such as an upper surface and a lower surface, have a surface area of ​​approximately any one of 20 mm2, 21 mm2, 22 mm2, 23 mm2, 24 mm2, 25 mm2, 26 mm2, 27 mm2, 28 mm2, 29 mm2, 30 mm2, 31 mm2, 32 mm2, 33 mm2, 34 mm2 35 mm2, 36 mm2, 37 mm2, 38 mm2, 39 mm2, 40 mm2, 41 mm2, 42 mm2 43 mm2, 44 mm2, 45 mm2, 46 mm2, 47 mm2, 48 mm2, 49 mm2, 50 mm2 51 mm2, 52 mm2, 53 mm2, 54 mm2, 55 mm2, 56 mm2, 57 mm2, 58 mm2 59 mm2, 60 mm2, 65 mm2, 70 mm2, 80 mm2, 85 mm2, 90 mm2, 95 mm2 100 mm2, 110 mm2, 120 mm2, 130 mm2, 140 mm2, 150 mm2, 160 mm2, 170 mm2, 180 mm2, 190 mm2, 200 mm2, 225 mm2, 250 mm2, 275 mm2, 300 mm2, 325 mm2, 350 mm2, 375 mm2or 400 mm2.

[0138] In some embodiments, the surface(s) of the drug component exposed to a body fluid is / are substantially consistent throughout the thickness of the drug component (as determined by the distance of the drug component substantially perpendicular to an upper and / or lower surface), for example, as the drug component erodes, the surface(s) exposed to the body fluid has / have the same surface area. In some embodiments, the area of ​​the surface(s) of the drug component exposed to a body fluid is / are different at two or more points, for example, as the drug component erodes, the surface(s) exposed to the body fluid changes by increasing and / or decreasing the surface area during the erosion of the component.In some embodiments, the shape of the drug component's surface(s) exposed to a body fluid is consistent throughout the thickness of the drug component; for example, as the drug component erodes, the surface(s) exposed to the body fluid retain(s) the same shape. Petition 870250088298, dated 09 / 29 / 2025, p. 102 / 266 86 / 181 In some embodiments, the shape of the drug component's surface(s) exposed to a body fluid is different at two or more points. In some embodiments, the drug component comprises a lower surface with a surface area substantially identical to that of an upper surface of the drug component. In some embodiments, the drug component comprises a lower surface with a surface area different from that of an upper surface of the drug component.

[0139] In some embodiments, the surface of a drug component initially exposed to a body fluid, such as an upper surface or a lower surface, has a maximum cross-sectional dimension of about 5 mm to about 20 mm, such as any of about 5 mm to about 15 mm, about 6 mm to about 13 mm, or about 7 mm to about 11 mm. In some embodiments, the surface of a drug component initially exposed to a body fluid, such as an upper surface or a lower surface, has a maximum cross-sectional dimension of at least about 5 mm, such as at least about any of 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm.In some embodiments, the surface of a drug component initially exposed to a body fluid, such as an upper surface or a lower surface, has a maximum transverse dimension of less than about 20 mm, such as less than any of 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, or 5 mm. In some embodiments, the surface of a drug component initially exposed to a body fluid, such as an upper surface or a lower surface, has a maximum transverse dimension of about any of 5 mm. Petition 870250088298, dated 09 / 29 / 2025, page 103 / 266 87 / 181 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm or 20 mm.

[0140] In some embodiments, the surface of a drug component initially exposed to a body fluid, such as an upper surface or a lower surface, has a transverse dimension perpendicular to the maximum transverse dimension of about 1 mm to about 15 mm, such as any of about 2 mm to about 15 mm, about 2 mm to about 6 mm, or about 1 mm to about 5 mm. In some embodiments, the surface of a drug component initially exposed to a body fluid, such as an upper surface or a lower surface, has a transverse dimension perpendicular to the maximum transverse dimension of at least about 1 mm, such as at least about any of 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, or 15 mm.In some embodiments, the surface of a drug component initially exposed to a body fluid, such as an upper surface or a lower surface, has a transverse dimension perpendicular to the maximum transverse dimension of less than about 15 mm, such as less than about any of 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, 2 mm, or 1 mm. In some embodiments, the surface of a drug component initially exposed to a body fluid, such as an upper surface or a lower surface, has a transverse dimension perpendicular to the maximum transverse dimension of about any of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, or 15 mm.

[0141] In some embodiments, the drug component, such as a drug component layer, has a thickness of about 0.1 mm to about 5 mm, such as any of about Petition 870250088298, dated 09 / 29 / 2025, page 104 / 266 88 / 181 from 0.2 mm to about 2 mm, from about 0.5 mm to about 1.5 mm, or from about 0.8 mm to about 1.4 mm. In some embodiments, the drug component, such as a drug component layer, has a thickness of at least about 0.1 mm, such as at least about any of 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2.0mm, 2.2mm, 2.4mm, 2.6mm, 2.8mm, 3.0mm, 3.2mm, 3.4mm, 3.6mm, 3.8mm, 4.0mm, 4.2 mm, 4.4 mm, 4.6 mm, 4.8 mm, or 5 mm. In some embodiments, the drug component, such as a drug component layer, has a thickness less than about 5 mm, such as less than about any of 4.8 mm, 4.6 mm, 4.4 mm, 4.2 mm, 4.0 mm, 3.8 mm, 3.6 mm, 3.4 mm, 3.2 mm, 3.0 mm, 2.8 mm, 2.6mm, 2.4mm, 2.2mm, 2.0mm, 1.9mm, 1.8mm, 1.7mm, 1.6mm, 1.5mm, 1.4mm, 1.3mm, 1.2mm, 1.1mm, 1.0mm, 0.9mm, 0.8mm, 0.7 mm, 0.6 mm, 0.5 mm, 0.4 mm, 0.3 mm, 0.2 mm, or 0.1 mm. In some embodiments, the drug component, such as a drug component layer, has a thickness of approximately any one of 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2.0mm, 2.2mm, 2.4mm, 2.6mm, 2.8mm, 3.0mm, 3.2mm, 3.4mm, 3.6mm, 3.8mm, 4.0mm, 4.2mm, 4.4mm, 4.6mm, 4.8mm or 5mm.

[0142] In some embodiments, the drug component, such as a drug component layer, comprises an upper surface and a lower surface, wherein the thickness, as measured between the upper surface and the lower surface, is substantially consistent, such as within a range of 20% of an average thickness. Petition 870250088298, dated 09 / 29 / 2025, pp. 105 / 266 89 / 181

[0143] In some embodiments, the drug component has a drug mass portion (mp) of a drug of about 0.05 to about 0.6, such as any of about 0.05 to about 0.1, about 0.2 to about 0.5, about 0.3 to about 0.4 or about 0.3 to about 0.35. In some embodiments, the drug component has a drug mass portion (mp) of a drug of at least about 0.05, such as at least about any of 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55 or 0.6. In some embodiments, the drug component has a drug mass portion (mp) of a drug of less than about 0.6, such as less than about any of 0.55, 0.5, 0.45, 0.4, 0.35, 0.3, 0.25, 0.2, 0.15, 0.1, or 0.05. In some embodiments, the drug component has a drug mass portion (mp) of a drug of about any of 0.05, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, or 0.6.

[0144] In some embodiments, the drug component is configured for an immediate drug release profile, for example, the erodible material mixed with a drug erodes (dissolves) when it comes into contact with a body fluid (such as gastrointestinal fluids) to release the drug from the oral drug dosage form according to an immediate drug release profile. In some embodiments, the drug component erodes completely, such as from the point of contact with gastrointestinal fluids, in a period of about 1 minute to about 1 hour, such as any of about 5 minutes to about 30 minutes, about 5 minutes to about 20 minutes, or about 10 minutes to about 20 minutes.In some embodiments, the drug component erodes completely, such as from the point of contact with gastrointestinal fluids, in a period shorter than about 1 hour, such as less than about any of them. Petition 870250088298, dated 09 / 29 / 2025, pp. 106 / 266 90 / 181 minutes, 50 minutes, 45 minutes, 40 minutes, 35 minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, 10 minutes, 9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes, 2 minutes or 1 minute.

[0145] In some embodiments, the drug component is configured for a prolonged drug release profile, for example, the erodible material mixed with a drug erodes (dissolves) when it comes into contact with a body fluid (such as gastrointestinal fluids) to release the drug from the oral drug dosage form according to a prolonged drug release profile. In some embodiments, the drug component erodes completely, such as from the point of contact with gastrointestinal fluids, in a period of about 1 hour to about 7 hours, such as any of about 2 hours to about 4 hours, such as about 2 hours to about 3 hours.In some embodiments, the drug component erodes completely, such as from the point of contact with gastrointestinal fluids, over a period of at least about 1 hour, such as at least about 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours or 7 hours.

[0146] In some embodiments, the amount of a drug in a drug component is from about 0.5 mg to about 500 mg. In some embodiments, the amount of a drug in a drug component is about 1 mg or more, such as about any one of 5 mg or more, 10 mg or more, 15 mg or more, 20 mg or more, 25 mg or more, 30 mg or more, 35 mg or more, 40 mg or more, 45 mg or more, 50 mg or more, 55 mg or more, 60 mg or more, 65 mg or more, 70 mg or more, 75 mg or more, 80 mg or more, 85 mg or more, 90 mg or more, 95 mg or more, 100 mg or more, 110 mg or more, 120 mg or more, 130 mg or more, 140 mg or more, 150 mg or more, Petition 870250088298, dated 09 / 29 / 2025, page 107 / 266 91 / 181 160 mg or more, 170 200 mg or more, 210 240 mg or more, 250 280 mg or more, 290 320 mg or more, 330 360 mg or more, 370 400 mg or more, 410 440 mg or more, 450 mg or more, 180 mg or more, 220 mg or more, 260 mg or more, 300 mg or more, 340 mg or more, 380 mg or more, 420 mg or more, 460 mg or more, 190 mg or more, more, 230 mg or more, more, 270 mg or more, more, 310 mg or more, more, 350 mg or more, more, 390 mg or more, more, 430 mg or more, more, 470 mg or more, 480 mg or more, 490 mg or more, or 500 mg or more.

[0147] In some embodiments, the weight ratio between the drug component and the delay component is from about 1:10 to about 10:1, such as any of about 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1 or 9:1.

[0148] In some embodiments, the oral drug dosage form comprises one or more drug components. For example, in some embodiments, the oral dosage form comprises one drug component. In some embodiments, the oral drug dosage form comprises two drug components. In some embodiments, the oral drug dosage form comprises three drug components. In some embodiments, the oral drug dosage form comprises four drug components. In some embodiments, the oral drug dosage form comprises five drug components. In embodiments comprising more than one drug component, the drug components may be the same or different from each other, such as having the same or different shape, size and / or constitution.

[0149] In some embodiments, the drug component, such as a drug component layer, comprises a thermoplastic material, for example, a thermoplastic polymer. In some Petition 870250088298, dated 09 / 29 / 2025, page 108 / 266 92 / 181 embodiments, the drug component, such as a drug component layer, comprises a material comprising any one or more of a matrix material, a plasticizer or other additive, for example, a filler, a binder, a lubricant, a glide and a disintegrant.

[0150] In some embodiments, the drug component comprises one or more of the following: copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, hydroxypropylmethylcellulose acetate succinate, hypromellose acetate succinate, hydroxypropylmethylcellulose phthalate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose or dextran 70.

[0151] In some embodiments, the plasticizer is any one or more of the following: triethyl citrate, vitamin E succinate, polyethylene glycol, acetylated triethyl citrate, tributyl citrate, tributyl o-acetylcitrate, polyoxyl 15 hydroxystearate, PEG-40 hydrogenated castor oil, polyoxyl 35 castor oil, dibutyl sebacate, diethyl phthalate, glycerin, methyl 4-hydroxybenzoate, castor oil, oleic acid, triacetin, polyalkylene glycol, stearic acid, palmitic acid, malic acid, polyethylene glycol, PEG-32 lauroyl glycerides, poloxamer 188, poloxamer 407, acetyltributyl citrate, D-sorbitol, propylene glycol, diethyl phthalate, citric acid, behenate glyceryl, D-mannitol, polysorbate, sorbitan monostearate, sorbitan monooleate or polyoxyl 40 stearate.

[0152] In some embodiments, the other additive is any one or more of the following: acacia, alginate, alginic acid, aluminum acetate, butylparaben, butylated hydroxytoluene, citric acid, calcium carbonate, Petition 870250088298, dated 09 / 29 / 2025, p. 109 / 266 93 / 181 candelilla wax, croscarmellose sodium, confectioners' sugar, colloidal silicon dioxide, cellulose, simple or anhydrous calcium phosphate, carnauba wax, corn starch, calcium carboxymethylcellulose, disodium ethylenediaminetetraacetic acid, dehydrated calcium hydrogen phosphate, cetylpyridinium chloride, dibasic calcium phosphate, tribasic calcium phosphate, dibasic calcium phosphate, disodium hydrogen phosphate, dimethicone, erythrosine sodium, ethylenediaminetetraacetic acid, gelatin, glyceryl monooleate, iron oxide, ferric oxide, yellow iron oxide, red iron oxide, lactose (aqueous, anhydrous, monohydrate or spray-dried), microcrystalline cellulose, magnesium carbonate, magnesium oxide, methylparaben, polysorbate 80, propylparaben, potassium bicarbonate, potassium sorbate, potato starch, phosphoric acid, polyoxyethylene stearate (40), sodium starch glycolate, pregelatinized starch, croscarmellose sodium,Sodium lauryl sulfate, starch, silicon dioxide, sodium benzoate, sucrose, sorbic acid, sodium carbonate, sodium saccharin, sodium alginate, silica gel, sorbitan monooleate, sodium chloride, sodium metabisulfite, dehydrated sodium citrate, sodium starch, sodium carboxymethylcellulose, succinic acid, sodium propionate, titanium dioxide or talc. 2. Drugs in oral dosage forms

[0153] In some embodiments, the drug in a drug component of an oral drug dosage form described in this document may be any drug. In some embodiments, the drug is an anti-inflammatory agent, nonsteroidal anti-inflammatory agent, steroid, immunosuppressant, antibiotic, biological agent, antineoplastic agent, analgesic, anesthetic, anticonvulsant, antidiabetic agent, antihistamine, anti-infective, antineoplastic, antiparkinsonian agent, antirheumatic agent, appetite stimulant, appetite suppressant, blood modifier, bone metabolism modifier, Petition 870250088298, dated 09 / 29 / 2025, page 110 / 266 94 / 181 cardiovascular agent, central nervous system depressant, central nervous system stimulant, decongestant, dopamine receptor agonist, electrolyte, gastrointestinal agent, immunomodulator, muscle relaxant, narcotic, parasympathomimetic, sympathomimetic, sedative, hypnotic or vaccine. In some embodiments, the vaccine is a peptide-based vaccine or a nucleic acid-based vaccine, such as an mRNA-based vaccine. In some embodiments, the nucleic acid-based vaccine comprises RNA, such as transfer RNA (tRNA), ribosomal RNA (rRNA) or messenger RNA (mRNA).

[0154] In some embodiments, the anti-inflammatory agent is a JAK inhibitor. In some embodiments, the drug is a JAK inhibitor. A JAK inhibitor is an agent that interferes with the JAK-STAT signaling pathway, such as an inhibitor of one or more elements associated with the JAK-STAT signaling pathway (e.g., a JAKinib). Elements associated with the JAK-STAT signaling pathway, and inhibitors thereof, are known in the art. See, for example, Rawlings et al., J Cell Sci, 117, 2004; and Schwartz et al., Nat Rev Drug Discov, 17, 2017. In some embodiments, the JAK inhibitor is an inhibitor of any one or more of Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), Janus kinase 3 (JAK3), or tyrosine kinase 2 (TYK2). In some embodiments, the JAK inhibitor is an inhibitor of JAK1 and JAK3. In some embodiments, the JAK inhibitor is an inhibitor of JAK1, JAK3, and JAK2. In some embodiments, the JAK inhibitor is an inhibitor of JAK1, JAK3, JAK2, and TYK2.In some embodiments, the JAK inhibitor is a JAK1 and JAK2 inhibitor. In some embodiments, the JAK inhibitor is a JAK1, JAK2, and TYK2 inhibitor. In some embodiments, the JAK inhibitor is an inhibitor of all JAKs (a pan-JAK inhibitor). In some embodiments, the drug is a JAK inhibitor (including a JAK1 inhibitor and / or JAK2 inhibitor and / or JAK3 inhibitor), antagonist of... Petition 870250088298, dated 09 / 29 / 2025, p. 111 / 266 95 / 181 sphingosine 1-phosphate (S1P) receptor, S1P receptor regulator 1, S1P receptor regulator 5, a glucocorticoid receptor (GCR) antagonist, tyrosine kinase (TYK) 2 inhibitor, cyclooxygenase (COX) inhibitor, dihydrofolate reductase (DHFR) inhibitor, or epithelial-mesenchymal transition (EMT) inhibitor, or an agent that acts in any one or more of the above ways.

[0155] In some embodiments, the drug is an S1P receptor antagonist, such as amiselimod or a pharmaceutical salt thereof. In some embodiments, the drug is amiselimod hydrochloride.

[0156] In some embodiments, the drug is a JAK1 inhibitor and a TYK2 inhibitor, such as brepocitinib or a pharmaceutical salt thereof. In some embodiments, the drug is brepocitinib tosylate.

[0157] In some embodiments, the drug is a GCR antagonist, such as budesonide or a pharmaceutical salt thereof. In some embodiments, the drug is budesonide.

[0158] In some embodiments, the drug is a TYK2 inhibitor, such as deucravacitinib or a pharmaceutical salt thereof. In some embodiments, the drug is deucravacitinib hydrochloride.

[0159] In some embodiments, the drug is an S1P receptor 1 regulator, such as etrasimod or a pharmaceutical salt thereof. In some embodiments, the drug is etrasimod arginine.

[0160] In some embodiments, the drug is a JAK1 inhibitor, such as filgotinib or a pharmaceutical salt thereof. In some embodiments, the drug is filgotinib maleate.

[0161] In some embodiments, the drug is a JAK inhibitor, such as ivarmacitinib or a pharmaceutical salt thereof. In some embodiments, the drug is ivarmacitinib sulfate.

[0162] In some embodiments, the drug is a JAK1 inhibitor, JAK2 inhibitor, JAK3 inhibitor, and TYK2 inhibitor (for example, a Petition 870250088298, dated 09 / 29 / 2025, p. 112 / 266 96 / 181 pan-Janus kinase inhibitor), such as izencitinib or a pharmaceutical salt thereof. In some embodiments, the drug is izencitinib.

[0163] In some embodiments, the drug is a COX inhibitor and a DHFR inhibitor, such as mesalamine or a pharmaceutical salt thereof. In some embodiments, the drug is mesalamine.

[0164] In some embodiments, the drug is an S1P receptor 1 regulator and an S1P receptor 5 regulator, such as ozanimod or a pharmaceutical salt thereof. In some embodiments, the drug is ozanimod hydrochloride.

[0165] In some embodiments, the drug is an EMT inhibitor and a JAK3 inhibitor, such as ritlecitinib or a pharmaceutical salt thereof. In some embodiments, the drug is ritlecitinib.

[0166] In some embodiments, the drug is a JAK1 inhibitor, a JAK2 inhibitor, and a JAK3 inhibitor, such as tofacitinib or a pharmaceutical salt thereof. In some embodiments, the drug is tofacitinib citrate.

[0167] In some embodiments, the drug is a JAK1 inhibitor, such as upadacitinib or a pharmaceutical salt thereof. In some embodiments, the drug is upadacitinib tartrate.

[0168] In some embodiments, the JAK inhibitor is selected from the group consisting of tofacitinib, abrocitinib, baricitinib, cerdulatinib, cucurbitacin I, decernotinib, fedratinib, filgotinib, gandotinib, itacitinib, lestaurtinib, momelotinib, oclacitinib, pacritinib, peficitinib, ruxolitinib, solcitinib, upadacitinib, BMS-986165, CHZ868 and SHR0302 or a pharmaceutically acceptable salt thereof. In some embodiments, the oral drug dosage form comprises a plurality of JAK inhibitors, wherein each JAK inhibitor is selected from the group consisting of tofacitinib, abrocitinib, baricitinib, cerdulatinib, cucurbitacin I, decernotinib, fedratinib, filgotinib, gandotinib, itacitinib, lestaurtinib, momelotinib, oclacitinib, pacritinib, Petition 870250088298, dated 09 / 29 / 2025, page 113 / 266 97 / 181 peficitinib, ruxolitinib, solcitinib, upadacitinib, B MS-986165, CHZ868 and SHR0302 or a pharmaceutically acceptable salt thereof.

[0169] In some embodiments, the JAK inhibitor is tofacitinib or a pharmaceutically acceptable salt thereof. In some embodiments, the JAK inhibitor is tofacitinib citrate, such as tofacitinib monocitrate. In some embodiments, the JAK inhibitor is tofacitinib tartrate, such as tofacitinib monotartrate. In some embodiments, the JAK inhibitor is tofacitinib malate, such as tofacitinib monomalate. In some embodiments, the JAK inhibitor is tofacitinib oxalate, such as tofacitinib monooxalate.

[0170] In some embodiments, the JAK inhibitor is a pharmaceutically acceptable salt in an amorphous form. In some embodiments, the JAK inhibitor is a pharmaceutically acceptable salt in a crystalline form.

[0171] In some forms, the anti-inflammatory agent is mesalazine, sulfasalazine, or balsalazide.

[0172] In some forms, the nonsteroidal anti-inflammatory agent is ibuprofen or diclofenac.

[0173] In some forms, the steroid is prednisolone, budesonide, or fluticasone.

[0174] In some modalities, the immunosuppressant is azathioprine, cyclosporine, or methotrexate.

[0175] In some embodiments, the biological agent is a peptide. In some embodiments, the peptide is a linear peptide, for example, insulin. In some embodiments, the peptide is a cyclic peptide, for example, octreotide. In some embodiments, the biological agent is an antibody, or a fragment thereof, such as a monoclonal antibody. In some embodiments, the biological agent is a nucleic acid, for example, DNA, RNA, analogues thereof, or combinations thereof. Petition 870250088298, dated 09 / 29 / 2025, page 114 / 266 98 / 181 of these. In some embodiments, the peptide is octreotide. In some embodiments, the antibody is infliximab, adalimumab, certolizumab pegol, golimumab, or ustekinumab.

[0176] In some embodiments, the antineoplastic agent is fluorouracil, methotrexate, dactinomycin, bleomycin, etoposide, taxol, vincristine, doxorubicin, cisplatin, daunorubicin, etoposide, raltitrexed or oxaliplatin or a combination thereof.

[0177] In some embodiments, the amount of a drug in an oral drug dosage form is from about 0.5 mg to about 500 mg. In some embodiments, the amount of a drug in a drug component is about 1 mg or more, such as about any one of 5 mg or more, 10 mg or more, 15 mg or more, 25 mg or more, 30 mg or more, 35 mg or more, 40 mg or more, 45 mg or more, 50 mg or more, 55 mg or more, 60 mg or more, 70 mg or more, 75 mg or more, 80 mg or more, 85 mg or more, 90 mg or more, 120 mg or more, 160 mg or more, 200 mg or more, 240 mg or more, 280 mg or more, 320 mg or more, 360 mg or more, 400 mg or more, 440 mg or more, 95 mg or more, 130 mg or more, 170 mg or more. mg or more, 210 mg or more, 250 mg or more, 290 mg or more, 330 mg or more, 370 mg or more, 410 mg or more, 450 mg or more, 100 mg or more, 140 mg or more, 180 mg or more, 220 mg or more, 260 mg or more, 300 mg or more, 340 mg or more, 380 mg or more, 420 mg or more,460 mg or more, 110 mg or more, 150 mg or more, 190 mg or more, 230 mg or more, 270 mg or more, 310 mg or more, 350 mg or more, 390 mg or more, 430 mg or more, 470 mg or more, 480 mg or more, 490 mg or more, or 500 mg or more. In some embodiments, the amount of a drug in a drug component is about 500 mg or less, such as about any one of 490 mg or less, 480 mg or less, 470 mg or less, 460 mg or less, 450 mg or less, 440 mg or less, 430 mg or less, Petition 870250088298, dated 09 / 29 / 2025, pp. 115 / 266 99 / 181 420 mg or less, 410 mg or less, 400 mg or less, 390 mg or less, 380 mg or less, 370 mg or less, 360 mg or less, 350 mg or less, 340 mg or less, 330 mg or less, 320 mg or less, 310 mg or less, 300 mg or less, 290 mg or less, 280 mg or less, 270 mg or less, 260 mg or less, 250 mg or less, 240 mg or less, 230 mg or less, 220 mg or less, 210 mg or less, 200 mg or less, 190 mg or less, 180 mg or less, 170 mg or less, 160 mg or less, 150 mg or less, 140 mg or less, 130 mg or less, 120 mg or less less, 110 mg or less, 100 mg or less, 90 mg or less, 80 mg or less, 70 mg or less, 60 mg or less, 50 mg or less, 40 mg or less, 30 mg or less, 20 mg or less, 10 mg or less, 5 mg or less, or 1 mg or less.In some embodiments, the amount of a drug in a drug component is approximately any one of 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg. 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg, 400 mg, 410 mg, 420 mg, 430 mg, 440 mg, 450 mg, 460 mg, 470 mg, 480 mg, 490 mg or 500 mg. 3. Delay components

[0178] The oral drug dosage forms described in this document comprise a delay component configured to control, such as preventing and / or inhibiting, the release of a drug from the oral drug dosage form so as to release the drug at the desired site in the colon. As described in this document, the delay component is not mixed with the drug of the drug component. In some embodiments, the delay components do not contain a Petition 870250088298, dated 09 / 29 / 2025, pp. 116 / 266 100 / 181 drug, such as an active pharmaceutical ingredient. In some embodiments, the delay component comprises another drug. In addition, aspects of the delay component may be mixed with another agent, such as a bacterial degradation moiety or an excipient.

[0179] In some embodiments, the delay component surrounds the drug component. In some embodiments, the delay component completely surrounds the drug component.

[0180] In some embodiments, the delay component (such as through aspects thereof) surrounds at least partially, for example, in layers, a drug component. For example, in some embodiments, the drug component is intercalated between two erodible delay layers, which in turn are intercalated between two pH-based enteric layers. In some embodiments, the delay component is formed by any number of layers of pH-based enteric layers and erodible delay layers. In some embodiments, when a drug component is at least partially surrounded, for example, intercalated, by layers of the delay component, the layers may form symmetrical or asymmetrical structures. For example, in some embodiments, the drug component is intercalated between two erodible delay layers, which in turn are intercalated between two pH-based enteric layers.In some embodiments, the drug component is sandwiched between two erodible retardant layers, wherein an additional erodible retardant layer is added to a surface distal to the drug component of one of the two erodible retardant layers, and wherein the drug component and the erodible retardant layers are sandwiched between two pH-based enteric layers. Petition 870250088298, dated 09 / 29 / 2025, p. 117 / 266 101 / 181 / '. pH-based enteric elements

[0181] The delay components described in this document comprise a pH-based enteric element, such as a layer of pH-based enteric element. In some embodiments, the pH-based enteric element comprises more than one layer of pH-based enteric material, such as two layers of a pH-based enteric material.

[0182] In some embodiments, the oral drug dosage form comprises one or more pH-based enteric elements, wherein the one or more pH-based enteric elements may be the same or different from each other, such as having the same or different shape, size and / or constitution. For example, in some embodiments, the oral drug dosage form comprises a first pH-based enteric element and a second pH-based enteric element. In some embodiments, the first pH-based enteric element and the second pH-based enteric element have different pHs, at which the respective materials begin to erode. In some embodiments, the oral drug dosage form is configured so that a first pH-based enteric element erodes before a second pH-based enteric element is exposed to a body fluid after administration to an individual.

[0183] The pH-based enteric element is configured to erode at or above a desired pH value. As recognized in the field, different regions of the human gastrointestinal tract have environments with different pHs. The use of such pH-based enteric elements helps control the erosion of this component from the oral drug dosage forms described in this document to a desired location in the gastrointestinal tract. In some embodiments, the pH-based enteric element erodes at a pH value between about 5.5 and about 8, such as between any of about 5.5 and about 7.5 and about Petition 870250088298, dated 09 / 29 / 2025, p. 118 / 266 102 / 181 from 6 to about 7. In some embodiments, the enteric pH-based element erodes at a pH value of, or greater than, about 5.5, such as about any one of 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9 or 8.

[0184] The pH-based enteric element can be formed using various materials with varying shapes and sizes. In some embodiments, the pH-based enteric element is a layer of a pH-based enteric material. In some embodiments, the pH-based enteric elements are configured to have surfaces, such as a surface exposed to a body fluid during the administration of the oral drug dosage form to a human subject, with a predetermined shape and surface area. For example, in some embodiments, the pH-based enteric element has a top surface and a bottom surface, where the top surface is exposed to a body fluid before the bottom surface. In some embodiments, the pH-based enteric element is a layer with a top surface and a bottom surface.In some embodiments, the upper surface of the pH-based enteric element is not flat; for example, it comprises certain features that extend beyond a top surface plane or surface tolerance limit (as measured between two parallel planes), such as to reduce the adhesion of the pH-based enteric element, or a portion thereof, to an internal part of the human body. In some embodiments, the upper surface of the pH-based enteric element, or at least a portion thereof, is flat or is within a surface tolerance limit.

[0185] In some embodiments, the pH-based enteric element surrounds the drug component. In these embodiments, there may be no additional material between the pH-based enteric element or there may be additional material between the pH-based enteric element. Petition 870250088298, dated 09 / 29 / 2025, p. 119 / 266 103 / 181 and the drug component, for example, the presence of an erodible retardant element.

[0186] The surfaces of a pH-based enteric element, such as a pH-based enteric element layer, based on the surface exposed to a body fluid after administration, can have any shape. In some embodiments, the surface has the shape of a capsule, circle, oval, projectile shape, arrowhead shape, triangle, arched triangle, square, arched square, rectangle, arched rectangle, rhombus, pentagon, hexagon, octagon, crescent moon, almond, or a combination thereof.

[0187] In some embodiments, the surface of a pH-based enteric element, such as a pH-based enteric element layer, has a surface area of ​​about 10 mm2 to about 400 mm2, such as any of about 20 mm2 to about 200 mm2, about 20 mm2 to about 100 mm2, about 20 mm2 to about 60 mm2, about 30 mm2 to about 50 mm2. In some embodiments, the surface of a pH-based enteric element has a surface area of ​​at least about 20 mm², such as at least about any one of 22 mm², 24 mm², 26 mm², 28 mm², 30 mm², 32 mm², 33 mm², 34 mm², 36 mm², 38 mm², 40 mm², 42 mm², 44 mm², 46 mm², 48 mm², 50 mm², 52 mm², 54 mm², 56 mm², 58 mm², 60 mm², 65 mm², 70 mm², 80 mm², 85 mm², 90 mm², 95 mm², 100 mm², 110 mm², 120 mm², 130 mm², 140 mm², 150 mm², 160 mm2, 170 mm2, 180 mm2, 190 mm2, 200 mm2, 225 mm2, 250 mm2, 275 mm2, 300 mm2, 325 mm2, 350 mm2, 375 mm2or 400 mm2.In some embodiments, the surface area of ​​a pH-based enteric element is less than about 400 mm2, such as less than about any of the following: 400 mm2, 375 mm2, 350 mm2, 325 mm2, 300 mm2, 275 mm2, 250 mm2, 225 mm2, 200 mm2, 190 mm2, 180 mm2, 170 mm2, 160 mm2, 150 mm2, 140 mm2, 130 mm2, 120 mm2. Petition 870250088298, dated 09 / 29 / 2025, pp. 120 / 266 104 / 181 110 mm2, 100 mm2, 95 mm2, 90 mm2, 85 mm2, 80 mm2, 75 mm2, 70 mm2, 65 mm2, 60 mm2, 58 mm2, 56 mm2, 54 mm2, 52 mm2, 50 mm2, 48 mm2, 46 mm2, 44 mm2, 42 mm2, 40 mm2, 38 mm2, 36 mm2, 34 mm2, 32 mm2, 30 mm2, 28 mm2, 26 mm2, 24 mm2, 22 mm2or 20 mm2. In some embodiments, the surface area of ​​a pH-based enteric element is approximately any one of 20 mm², 21 mm², 22 mm², 23 mm², 24 mm², 25 mm², 26 mm², 27 mm², mm², 29 mm², 30 mm², 31 mm², 32 mm², 33 mm², 34 mm², 35 mm², 37 mm², 38 mm², 39 mm², 40 mm², 41 mm², 42 mm², 43 mm², 45 mm², 46 mm², 47 mm², 48 mm², 49 mm², 50 mm², 51 mm², 53 mm², 54 mm², 55 mm², 56 mm², 57 mm², 58 mm², 59mm mm2, 65 mm2, 70 mm2, 80 mm2,85 mm2, 90 mm2, 95 mm2,100 mm2, 110 mm2, 120 mm2, 130 mm2, 140 mm2, 150 mm2, 160 mm2, 170 mm2, 180 mm2, 190 mm2, 200 mm2, 225 mm2, 250 mm2, 275 mm2, 300 mm2, 325 mm2, 350 mm2, 375 mm2or 400 mm2.

[0188] In some embodiments, the surface area of ​​a pH-based enteric element exposed to a body fluid is consistent throughout the thickness of the pH-based enteric element, for example, as a pH-based enteric element erodes, the surface exposed to the body fluid has the same surface area. In some embodiments, the surface area of ​​a pH-based enteric element exposed to a body fluid is different at two or more points, for example, as a pH-based enteric element erodes, the surface exposed to the body fluid changes, such as increasing and / or decreasing the surface area during the erosion of a pH-based enteric element. In some embodiments, the shape of the surface of a pH-based enteric element exposed to a body fluid is consistent throughout the thickness of the pH-based enteric element.In some modalities, the shape of a pH-based enteric element surface exposed to a body fluid differs at two or more points. Petition 870250088298, dated 09 / 29 / 2025, pp. 121 / 266 105 / 181

[0189] In some embodiments, the surface of a pH-based enteric element, such as a pH-based enteric element layer, has a maximum transverse dimension of about 5 mm to about 20 mm, such as any of about 5 mm to about 15 mm, about 6 mm to about 13 mm, or about 7 mm to about 11 mm. In some embodiments, the surface of a pH-based enteric element has a maximum transverse dimension of at least about 5 mm, such as at least about any of 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm. In some embodiments, the surface of a pH-based enteric element has a maximum transverse dimension smaller than about 20 mm, such as smaller than about any one of 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, or 5 mm.In some embodiments, the surface of a pH-based enteric element has a maximum transverse dimension of approximately any one of 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm.

[0190] In some embodiments, the surface of a pH-based enteric element, such as a pH-based enteric element layer, has a transverse dimension perpendicular to the maximum transverse dimension of about 1 mm to about 15 mm, such as any of about 2 mm to about 10 mm, about 2 mm to about 6 mm, or about 1 mm to about 5 mm. In some embodiments, the surface of a pH-based enteric element has a transverse dimension perpendicular to the maximum transverse dimension of at least about 1 mm, such as at least about any of 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, Petition 870250088298, dated 09 / 29 / 2025, pp. 122 / 266 106 / 181 mm, 13 mm, 14 mm, or 15 mm. In some embodiments, the surface of a pH-based enteric element has a transverse dimension perpendicular to the maximum transverse dimension that is less than about 15 mm, such as less than about any of 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, 2 mm, or 1 mm. In some embodiments, the surface of a pH-based enteric element has a transverse dimension perpendicular to the maximum transverse dimension that is about any of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, or 15 mm.

[0191] In some embodiments, the pH-based enteric element layer has a thickness of about 0.1 mm to about 5 mm, such as any of about 0.2 mm to about 2 mm, about 0.5 mm to about 1.5 mm, or about 0.8 mm to about 1.4 mm. In some embodiments, the pH-based enteric element layer has a thickness of at least about 0.1 mm, such as at least about any of 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2.0mm, 2.2mm, 2.4mm, 2.6mm, 2.8mm, 3.0mm, 3.2mm, 3.4mm, 3.6mm, 3.8mm, 4.0mm, 4.2 mm, 4.4 mm, 4.6 mm, 4.8 mm, or 5 mm. In some embodiments, the pH-based enteric element layer has a thickness less than about 5 mm, such as less than about any of 4.8 mm, 4.6 mm, 4.4 mm, 4.2 mm, 4.0 mm, 3.8 mm, 3.6 mm, 3.4mm, 3.2mm, 3.0mm, 2.8mm, 2.6mm, 2.4mm, 2.2mm, 2.0mm, 1.9mm, 1.8mm, 1.7mm, 1.6mm, 1.5mm, 1.4mm, 1.3mm, 1.2mm, 1.1mm, 1.0mm, 0.9mm, 0.8mm, 0.7mm, 0.6mm, 0.5mm, 0.4mm, 0.3 mm, 0.2 mm, or 0.1 mm. In some embodiments, the pH-based enteric element layer has a thickness of approximately any one of 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, Petition 870250088298, dated 09 / 29 / 2025, pp. 123 / 266 107 / 181 0.7mm, 0.8mm, 0.9mm, 1.1mm, 1.2mm, 1.3mm, 1.4mm, 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2.0mm, 2.2mm, 2.4mm, 2.6mm, 2.8mm, 3.0mm, 3.2mm, 3.4mm, 3.6mm, 3.8mm, 4.0mm, 4.2mm, 4.4mm, 4.6mm, 4.8mm or 5mm.

[0192] In some embodiments, the pH-based enteric element layer comprises an upper surface and a lower surface, wherein the thickness, as measured between the upper surface and the lower surface, is substantially consistent, such as within a range of 20% of an average thickness.

[0193] In some embodiments, the pH-based enteric element, such as a pH-based enteric element layer, comprises a thermoplastic material, such as a thermoplastic polymer. In some embodiments, the pH-based enteric element, such as a pH-based enteric element layer, comprises a material comprising any one or more of a matrix material, a plasticizer or other additive, for example, a filler, a binder, a lubricant, a slip agent and a disintegrant.

[0194] In some embodiments, the pH-based enteric element comprises one or more of the following: stearic acid, copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, crospovidone, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, hydroxypropylmethylcellulose phthalate, methylcellulose, methacrylic acid copolymer, poly(methacrylic acid-ethyl acrylate), poly(butyl methacrylate-(2-dimethylaminoethyl)-methyl methacrylate-co-methacrylate), poly(dimethylaminoethyl methacrylate-methacrylic esters), poly(ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate-chloride), poly(methyl acrylate-methacrylate methyl-co-methacrylic acid), poly(methacrylic acid-co-methylmethacrylate), poly(methacrylic acid-ethyl acrylate), poly( Petition 870250088298, dated 09 / 29 / 2025, pp. 124 / 266 108 / 181 methacrylate-co-methyl methacrylate), polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, hydroxypropylmethylcellulose acetate succinate or hypromellose acetate succinate, methacrylic ester copolymer, ammonium alkyl methacrylate copolymer, ethylcellulose, polyvinyl acetate and polyvinylpyrrolidone, polyvinyl acetal diethyl aminolactate, polyvinyl acetal diethyl amino lactate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose, dextran 70 or maltose.

[0195] In some embodiments, the plasticizer is one or more of the following: triethyl citrate, vitamin E succinate, polyethylene glycol, acetylated triethyl citrate, tributyl citrate, tributyl o-acetylcitrate, polyoxyl 15 hydroxystearate, PEG-40 hydrogenated castor oil, polyoxyl 35 castor oil, dibutyl sebacate, diethyl phthalate, glycerin, methyl 4-hydroxybenzoate, castor oil, oleic acid, triacetin, polyalkylene glycol, stearic acid, palmitic acid, malic acid, polyethylene glycol, PEG-32 lauroyl glycerides, poloxamer 188, poloxamer 407, acetyltributyl citrate, D-sorbitol, propylene glycol, diethyl phthalate, citric acid, behenate glyceryl, D-mannitol, polysorbate, sorbitan monostearate, sorbitan monooleate or polyoxyl 40 stearate.

[0196] In some embodiments, the other additive is any one or more of the following: acacia, alginate, alginic acid, aluminum acetate, butylparaben, butylated hydroxytoluene, citric acid, calcium carbonate, candelilla wax, croscarmellose sodium, confectioners' sugar, colloidal silicon dioxide, cellulose, simple or anhydrous calcium phosphate, carnauba wax, corn starch, calcium carboxymethylcellulose, calcium disodium ethylenediaminetetraacetic acid, dehydrated calcium hydrogen phosphate, cetylpyridinium chloride, dibasic calcium phosphate, tribasic calcium phosphate, dibasic calcium phosphate, disodium hydrogen phosphate, Petition 870250088298, dated 09 / 29 / 2025, pp. 125 / 266 109 / 181 dimethicone, erythrosine sodium, ethylenediaminetetraacetic acid, gelatin, glyceryl monooleate, iron oxide, ferric oxide, yellow iron oxide, red iron oxide, lactose (aqueous, anhydrous, monohydrate or spray-dried), microcrystalline cellulose, magnesium carbonate, magnesium oxide, methylparaben, polysorbate 80, propylparaben, potassium bicarbonate, potassium sorbate, potato starch, phosphoric acid, polyoxyethylene stearate (40), sodium starch glycolate, pregelatinized starch, croscarmellose sodium, sodium lauryl sulfate, starch, silicon dioxide, sodium benzoate, sucrose, sorbic acid, sodium carbonate, sodium saccharin, sodium alginate, silica gel, sorbitan monooleate, sodium chloride, sodium metabisulfite, citrate of Dehydrated sodium, sodium starch, sodium carboxymethylcellulose, succinic acid, sodium propionate, titanium dioxide, or talc.

[0197] In some embodiments, wherein the retarding component does not comprise an erodible retarding element (for example, the retarding component consists essentially of a pH-based enteric element), the erodible material of the pH-based enteric element comprises one or more of hypromellose acetate succinate, hydroxypropylmethylcellulose phthalate, cellulose acetate propionate (CAP), poly(ethyl methacrylic acid-co-acrylate) or polyvinyl acetate phthalate (PVAP). In some embodiments, the hypromellose acetate succinate is HPMCAS LG / LF, HPMCAS MG / MF or HPMCAS HG / LF. In some embodiments, the hydroxypropylmethylcellulose phthalate is HPMCP HP-50 or HPMCP HP-55. In some embodiments, poly(ethyl methacrylic acid-co-acrylate) is Eudragit L100-55 or Eudragit L100. Erodible retardant elements

[0198] In certain embodiments, the oral drug dosage forms provided in this document comprise an erodible retardant element comprising an erodible material, such as being different from or the same as the erodible material of a drug component. Petition 870250088298, dated 09 / 29 / 2025, pp. 126 / 266 110 / 181 Generally, the erodible delay element is situated within an oral drug dosage form such that the erodible delay element is not exposed to bodily fluids after administration to an individual until erosion, such as substantially complete erosion, of a pH-based enteric element occurs. In some embodiments, the delay components described herein comprise an erodible delay element, such as a layer of erodible delay element. In some embodiments, the erodible delay element comprises more than one layer of an erodible delay material, such as two layers of an erodible delay material. In some embodiments, the oral drug dosage form comprises one or more erodible delay elements, wherein the one or more erodible delay elements may be the same or different from each other, such as having the same or different shape, size, and / or constitution.

[0199] In some embodiments, the erodible retardant element surrounds the drug component. In these embodiments, there may be no or no additional material between the erodible retardant element and the drug component.

[0200] The erodible retardant element is configured to erode over a predetermined period after exposure to a body fluid, such as after the erosion, such as the substantially complete erosion, of a pH-based enteric element or a layer thereof. In some embodiments, the erodible retardant element erodes, such as substantially eroding to expose another component of an oral drug dosage form, over a period of about 1 minute to about 7 hours. In some embodiments, the erodible retardant element erodes, such as substantially eroding to expose another component of an oral drug dosage form, over a period Petition 870250088298, dated 09 / 29 / 2025, pp. 127 / 266 111 / 181 of at least about 5 minutes, such as at least about any one of 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, or 7 hours. The erosion timing of the erodible retarding element, or a layer thereof, may be based on several factors, including composition and thickness.

[0201] The erodible retarding element may be formed using numerous materials with varying shapes and sizes. In some embodiments, the erodible retarding element is a layer of an erodible retarding material. In some embodiments, the erodible retardant elements are configured to have surfaces, such as a surface exposed to a body fluid during the administration of an oral drug dosage form to a human subject, with a predetermined shape and surface area.For example, in some embodiments, the erodible retardant element has an upper surface and a lower surface, wherein the upper surface is exposed to a body fluid before the lower surface. In some embodiments, the erodible retardant element is a layer with an upper surface and a lower surface. In some embodiments, the upper surface of the erodible retardant element is not flat, for example, it comprises certain features that extend beyond a top surface plane or a surface tolerance limit (as measured between two parallel planes). In some embodiments, the upper surface of the erodible retardant element, or at least a part thereof, is flat or lies within a surface tolerance limit.

[0202] The surfaces of an erodible retardant element, such as an erodible retardant layer, based on the surface exposed to a body fluid after administration, can have any shape. In some embodiments, the surface has the shape of a Petition 870250088298, dated 09 / 29 / 2025, pp. 128 / 266 112 / 181 capsule, circle, oval, projectile shape, arrowhead shape, triangle, arched triangle, square, arched square, rectangle, arched rectangle, rhombus, pentagon, hexagon, octagon, crescent moon, almond or a combination thereof.

[0203] In some embodiments, the surface of an erodible retardant element, such as an erodible retardant layer, has a surface area of ​​about 10 mm2 to about 400 mm2, such as any of about 20 mm2 to about 200 mm2, about 20 mm2 to about 100 mm2, about 20 mm2 to about 60 mm2, about 30 mm2 to about 50 mm2. In some embodiments, the surface of an erodible retardant element has a surface area of ​​at least about 20 mm², such as at least about any one of 22 mm², 24 mm², 26 mm², 28 mm², 30 mm², 32 mm², 33 mm², 34 mm², 36 mm², 38 mm², 40 mm², 42 mm², 44 mm², 46 mm², 48 mm², 50 mm², 52 mm², 54 mm², 56 mm², 58 mm², 60 mm², 65 mm², 70 mm², 80 mm², 85 mm², 90 mm², 95 mm², 100 mm², 110 mm², 120 mm², 130 mm², 140 mm², 150 mm², 160 mm2, 170 mm2, 180 mm2, 190 mm2, 200 mm2, 225 mm2, 250 mm2, 275 mm2, 300 mm2, 325 mm2, 350 mm2, 375 mm2or 400 mm2.In some embodiments, the surface area of ​​an erodible retardant element is less than about 400 mm², such as less than about any of the following: 400 mm², 375 mm², 350 mm², 325 mm², 300 mm², 275 mm², 250 mm², 225 mm², 200 mm², 190 mm², 180 mm², 170 mm², 160 mm², 150 mm², 140 mm², 130 mm², 120 mm², 110 mm², 100 mm², 95 mm², 90 mm², 85 mm², 80 mm², 75 mm², 70 mm², 65 mm², 60 mm², mm², 56 mm², 54 mm², 52 mm². 50 mm2, 48 mm2, 46 mm2, 44 mm2, mm2, 40 mm2, 38 mm2, 36 mm2, 34 mm2, 32 mm2, 30 mm2, 28 mm2, mm2, 24 mm2, 22 mm2 or 20 mm2. In some embodiments, the surface of an erodible retardant element has a surface area of ​​approximately any one of 20 mm2, 21 mm2, 22 mm2, 23 mm2,. Petition 870250088298, dated 09 / 29 / 2025, pp. 129 / 266 113 / 181 mm2, 25 mm2, 26 mm2, 27 mm2, 28 mm2, 29 mm2, 30 mm2, 31 mm2, mm2, 33 mm2, 34 mm2, 35 mm2, 36 mm2, 37 mm2, 38 mm2, 39 mm2, mm2, 41 mm2, 42 mm2, 43 mm2, 44 mm2, 45 mm2, 46 mm2, 47 mm2, mm2, 49 mm2, 50 mm2, 51 mm2, 52 mm2, 53 mm2, 54 mm2, 55 mm2, mm2, 57 mm2, 58 mm2, 59 mm2, 60 mm2, 65 mm2, 70 mm2, 80 mm2, mm2, 90 mm2, 95 mm2, 100 mm2, 110 mm2, 120 mm2, 130 mm2, 140 mm2, 150 mm2, 160 mm2, 170 mm2, 180 mm2, 190 mm2, 200 mm2, 225 mm2, 250 mm2, 275 mm2, 300 mm2, 325 mm2, 350 mm2, 375 mm2 or 400 mm2.

[0204] In some embodiments, the surface area of ​​an erodible retardant element exposed to a body fluid is consistent throughout the thickness of the erodible retardant element, for example, as an erodible retardant element erodes, the surface exposed to the body fluid has the same surface area. In some embodiments, the surface area of ​​an erodible retardant element exposed to a body fluid is different at two or more points, for example, as an erodible retardant element erodes, the surface exposed to the body fluid changes, such as increasing and / or decreasing the surface area during the erosion of the erodible retardant element. In some embodiments, the shape of the surface of an erodible retardant element exposed to a body fluid is consistent throughout the thickness of the erodible retardant element.In some modalities, the shape of a surface of an erodible retardant element exposed to a body fluid is different at two or more points.

[0205] In some embodiments, the surface of an erodible retardant element, such as an erodible retardant element layer, has a maximum transverse dimension of about 5 mm to about 20 mm, such as any of about 5 mm to about 15 mm, about 6 mm to about 13 mm or about 7 mm to about 11 mm. Petition 870250088298, dated 09 / 29 / 2025, pp. 130 / 266 114 / 181 In some embodiments, the surface of an erodible retardant element has a maximum transverse dimension of at least about 5 mm, such as at least about any one of 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm. In some embodiments, the surface of an erodible retardant element has a maximum transverse dimension smaller than about 20 mm, such as smaller than about any one of 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, or 5 mm. In some embodiments, the surface of an erodible retardant element has a maximum transverse dimension of approximately any one of 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm.

[0206] In some embodiments, the surface of an erodible retardant element, such as an erodible retardant layer, has a transverse dimension perpendicular to the maximum transverse dimension of about 1 mm to about 15 mm, such as any of about 2 mm to about 10 mm, about 2 mm to about 6 mm, or about 1 mm to about 5 mm. In some embodiments, the surface of an erodible retardant element has a transverse dimension perpendicular to the maximum transverse dimension of at least about 1 mm, such as at least about any of 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, or 15 mm. In some embodiments, the surface of an erodible retardant element has a transverse dimension perpendicular to the maximum transverse dimension that is less than about 15 mm, such as less than about any of 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, 2 mm, or 1 mm.In some sports, the surface of... Petition 870250088298, dated 09 / 29 / 2025, pp. 131 / 266 115 / 181 an erodible retardant element has a transverse dimension perpendicular to the maximum transverse dimension of approximately any one of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm or 15 mm.

[0207] In some embodiments, the erodible retardant layer has a thickness of about 0.1 mm to about 5 mm, such as any of about 0.2 mm to about 2 mm, about 0.5 mm to about 1.5 mm, about 0.6 mm to about 1.6 mm or about 0.8 mm to about 1.4 mm. In some embodiments, the erodible retardant layer has a thickness of at least about 0.1 mm, such as at least about any of 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8mm, 1.9mm, 2.0mm, 2.2mm, 2.4mm, 2.6mm, 2.8mm, 3.0mm, 3.2mm, 3.4mm, 3.6mm, 3.8mm, 4.0mm, 4.2mm, 4.4mm, 4.6mm, 4.8 mm or 5 mm. In some embodiments, the erodible retardant layer has a thickness less than about 5 mm, such as less than about any of 4.8 mm, 4.6 mm, 4.4mm, 4.2mm, 4.0mm, 3.8mm, 3.6mm, 3.4mm, 3.2mm, 3.0mm, 2.8mm, 2.6mm, 2.4mm, 2.2mm, 2.0mm, 1.9mm, 1.8mm, 1.7mm, 1.6mm, 1.5mm, 1.4mm, 1.3mm, 1.2mm, 1.1mm, 1.0mm, 0.9mm, 0.8 mm, 0.7 mm, 0.6 mm, 0.5 mm, 0.4 mm, 0.3 mm, 0.2 mm, or 0.1 mm. In some embodiments, the erodible retardant layer has a thickness of approximately any one of 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.1 mm, 1.2mm, 1.3mm, 1.4mm, 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2.0mm, 2.2mm, 2.4mm, 2.6mm, 2.8mm, 3.0mm, 3.2mm, 3.4mm, 3.6mm, 3.8mm, 4.0mm, 4.2mm, 4.4mm, 4.6mm, 4.8mm or 5mm. In some embodiments, the erodible retardant layer has a thickness of approximately any of 0.6 mm, 0.7 mm, Petition 870250088298, dated 09 / 29 / 2025, pp. 132 / 266 116 / 181 0.8 mm, 0.9 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, or 1.6 mm. The inventors of the present invention observed that when the thickness of the delayed layer is thick, the surface of the delayed layer tends to gel, facilitating passage through the gastrointestinal tract without releasing the drug in the colon, whereas when the thickness of the delayed layer is thin, some surfaces of the delayed layer tend to be damaged and release the drug prematurely due to irregular fluid flow. Therefore, it is necessary to create a delayed layer with the correct thickness to ensure that the drug is released in the colon without gelation of the delayed layer and that it is not affected by body fluids for premature drug release.

[0208] In some embodiments, the erodible retardant layer comprises an upper surface and a lower surface, wherein the thickness, as measured between the upper surface and the lower surface, is substantially consistent, such as within a range of 20% of an average thickness.

[0209] In some embodiments, the erodible retardant element, such as an erodible retardant element layer, comprises a thermoplastic material, such as a thermoplastic polymer. In some embodiments, the erodible retardant element, such as an erodible retardant element layer, comprises a material comprising any one or more of a matrix material, a plasticizer or other additive, for example, a filler, a binder, a lubricant, a glide, an inorganic salt and a disintegrant. The inventors of the present invention have observed that the erodible retardant layer of the present invention is capable of constituting erosion, for example, eroding layer by layer, without gelation resulting in delayed drug release. Petition 870250088298, dated 09 / 29 / 2025, pp. 133 / 266 117 / 181

[0210] In some embodiments, the thermoplastic polymer comprises one or more of the following: stearic acid, medium-chain triglycerides, glyceryl distearate, propylene glycol monolaurate, propylene glycol caprylate, polyoxyl-6 oleoyl glycerides, PEG-6 stearate, PEG-32 stearate, polyoxyl-6 linoleoyl glycerides, polyoxyl-32 lauroyl glycerides, polyoxyl-8 caprylocaproyl glycerides, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan oleate, glyceryl monolinoleate, copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, crospovidone, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, hydroxypropylmethylcellulose phthalate, methylcellulose, methacrylic acid copolymer, poly(methacrylic acid-ethyl acrylate), poly(butyl methacrylate-(2-dimethylaminoethyl)-methyl methacrylate-co-methacrylate),poly(dimethylaminoethylmethacrylate-methacrylic copolymers), poly(ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate copolymer), poly(methyl acrylate-methyl methacrylate-methacrylic acid copolymer), poly(methacrylic acid-methyl methacrylate copolymer), poly(methacrylic acid-methyl methacrylate copolymer), polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, hydroxypropylmethylcellulose acetate succinate or hypromellose acetate succinate, methacrylic ester copolymer, ammonium alkyl methacrylate copolymer, ethylcellulose, polyvinyl acetate and polyvinylpyrrolidone, polyvinyl acetal diethyl aminolactate, polyvinyl acetal diethyl amino lactate, maltitol, lactose monohydrate, xylitol, isomalt,sucrose, glucose, dextran 70, maltose, lauroyl polyoxyl-32 glycerides, caprylocaproyl polyoxyl-8 glycerides, castor oil polyoxyl, Petition 870250088298, dated 09 / 29 / 2025, pp. 134 / 266 118 / 181 (35), vitamin E succinate polyethylene glycol, hydrogenated castor oil PEG-40, glyceryl monolinoleate or glyceryl dibehenate. In some embodiments, the thermoplastic polymer comprises one or more of hydroxypropylcellulose and vitamin E succinate polyethylene glycol. In some embodiments, the weight of the thermoplastic polymer is 60% to 85% of the weight of the erodible retardant element.

[0211] In some embodiments, the plasticizer is any one or more of the following: triethyl citrate, vitamin E succinate, polyethylene glycol, acetylated triethyl citrate, tributyl citrate, tributyl o-acetylcitrate, polyoxyl 15 hydroxystearate, PEG-40 hydrogenated castor oil, polyoxyl 35 castor oil, dibutyl sebacate, diethyl phthalate, glycerin, methyl 4-hydroxybenzoate, castor oil, oleic acid, triacetin, polyalkylene glycol, stearic acid, palmitic acid, malic acid, polyethylene glycol, PEG-32 lauroyl glycerides, poloxamer 188, poloxamer 407, acetyltributyl citrate, D-sorbitol, propylene glycol, diethyl phthalate, citric acid, behenate Glyceryl, D-mannitol, polysorbate, sorbitan monostearate, sorbitan monooleate, or polyoxyl 40 stearate. In some embodiments, the plasticizer is triethyl citrate. In some embodiments, the weight of the plasticizer is 5% to 20% of the weight of the erodible retarding element.In some applications, the weight of the plasticizer is 10% to 15% of the weight of the erodible retardant element.

[0212] In some embodiments, the inorganic salt is any one or more of calcium phosphate, calcium hydrogen phosphate, disodium hydrogen phosphate, sodium carbonate, sodium chloride, sodium phosphate, calcium hydrogen phosphate, calcium carbonate, calcium chloride, potassium phosphate, dipotassium hydrogen phosphate, potassium carbonate, and potassium chloride. In some embodiments, the inorganic salt is calcium hydrogen phosphate. In some embodiments, the weight of the inorganic salt Petition 870250088298, dated 09 / 29 / 2025, pp. 135 / 266 119 / 181 nico is 5% to 20% of the weight of the erodible retarding element. In some embodiments, the weight of the inorganic salt is 10% of the weight of the erodible retarding element.

[0213] In some embodiments, the other additive is any one or more of the following: acacia, alginate, alginic acid, aluminum acetate, butylparaben, butylated hydroxytoluene, citric acid, calcium carbonate, candelilla wax, croscarmellose sodium, confectioners' sugar, colloidal silicon dioxide, cellulose, simple or anhydrous calcium phosphate, carnauba wax, corn starch, calcium carboxymethylcellulose, calcium disodium ethylenediaminetetraacetic acid, dehydrated calcium hydrogen phosphate, cetylpyridinium chloride, calcium hydrophosphate, dibasic calcium phosphate, tribasic calcium phosphate, dibasic calcium phosphate, disodium hydrogen phosphate, dimethicone, erythrosine sodium, ethylenediaminetetraacetic acid, gelatin, glyceryl monooleate, iron oxide, ferric oxide, iron oxide Yellow, red iron oxide, lactose (aqueous, anhydrous, monohydrate or spray-dried), microcrystalline cellulose, magnesium carbonate, magnesium oxide, methylparaben,polysorbate 80, propylparaben, potassium bicarbonate, potassium sorbate, potato starch, phosphoric acid, polyoxyethylene stearate (40), sodium starch glycolate, pregelatinized starch, croscarmellose sodium, sodium lauryl sulfate, starch, silicon dioxide, sodium benzoate, sucrose, sorbic acid, sodium carbonate, sodium saccharin, sodium alginate, silica gel, sorbitan monooleate, sodium chloride, sodium metabisulfite, dehydrated sodium citrate, sodium starch, sodium carboxymethylcellulose, succinic acid, sodium propionate, titanium dioxide or talc. / / / '. Portion of bacterial degradation and elements of bacterial degradation

[0214] In certain embodiments, the oral drug dosage forms provided in this document comprise a portion of Petition 870250088298, dated 09 / 29 / 2025, pp. 136 / 266 120 / 181 Bacterial degradation. As described in this document, a bacterial degradation moiety is a moiety that can be digested by one or more bacteria present, or likely to be present, in an individual's colon. Such moieties may assist in the specific degradation in the colon of one or more aspects of an oral drug dosage form. In some embodiments, the bacterial degradation moiety is mixed into an aspect of an oral drug dosage form, such as an erodible retarding element or a drug component. In some embodiments, the retarding component further comprises a bacterial degradation element comprising an erodible material mixed with the bacterial degradation moiety.In some embodiments, where the oral drug dosage form comprises a bacterial degradation element, the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible retarding element, the erodible retarding element erodes before the bacterial degradation element, and the bacterial degradation element erodes before the drug component. In some embodiments, where the oral drug dosage form comprises a bacterial degradation element, the pH-based enteric element at least partially prevents the erosion of the erodible retarding element, the erodible retarding element at least partially prevents the erosion of the bacterial degradation element, and the bacterial degradation element at least partially prevents the erosion of the drug component.In some embodiments, the oral drug dosage form comprises one or more bacterial degradation elements, wherein the one or more bacterial degradation elements may be the same or different from each other, such as having the same or different shape, size and / or constitution. Petition 870250088298, dated 09 / 29 / 2025, pp. 137 / 266 121 / 181

[0215] In some embodiments, the bacterial degradation portion is digestible by one or more microorganisms present in the individual's colon. In some embodiments, the bacterial degradation portion comprises one or more saccharides. In some embodiments, the one or more saccharides comprise any one or more of sucrose, glucose, xylose, fructose, maltose, galactose, pectin, galactomannan, dextran, inulin, chitosan, carrageenan, cellulose acetate propionate (CAP), peptidoglycan, gellan, maxanthan gum, lentinan, psyllium polysaccharide, corn bran arabinoxylan, alginate, hyaluronic acid, fucoidan, shellac, agar, or maltodextrin.

[0216] In some embodiments, the oral drug dosage form comprises an amount of the bacterial degradation portion of about 0.5 mg to about 500 mg. In some embodiments, the amount of a bacterial degradation portion in an oral drug dosage form is about 1 mg or more, such as about any one of 5 mg or more, 10 mg or more, 15 mg or more, 20 mg or more, 25 mg or more, 30 mg or more, 35 mg or more, 40 mg or more, 45 mg or more, 50 mg or more, 55 mg or more, 60 mg or more, mg or more, 70 mg or more, 75 mg or more, 80 mg or more, 85 mg or more, 90 mg or more, 120 mg or more, 160 mg or more, 200 mg or more, 240 mg or more, 280 mg or more, 320 mg or more, 360 mg or more, 400 mg or more, 440 mg or more, 95 mg or more, 130 mg or more, 170 mg or more, 210 mg or more, 250 mg or more, 290 mg or more, 330 mg or more, 370 mg or more, 410 mg or more, 450 mg or more, 100 mg or more, 140 mg or more, 180 mg or more, 220 mg or more, 260 mg or more,300 mg or more, 340 mg or more, 380 mg or more, 420 mg or more, 460 mg or more, 110 mg or more, 150 mg or more, 190 mg or more, 230 mg or more, 270 mg or more, 310 mg or more, 350 mg or more, 390 mg or more, 430 mg or more, 470 mg or more, 480 mg or more, 490 mg or more, or 500 mg or more. In some, Petition 870250088298, dated 09 / 29 / 2025, pp. 138 / 266 122 / 181 modalities, the amount of a bacterial degradation portion in an oral drug dosage form is about 500 mg or less, such as about any one of 490 mg or less, 480 mg or less, 470 mg or less, 460 mg or less, 450 mg or less, 440 mg or less, 430 mg or less, 420 mg or less, 410 mg or less, 400 mg or less, 390 mg or less, 380 mg or less, 370 mg or less, 360 mg or less, 350 mg or less, 340 mg or less, 330 mg or less, 320 mg or less, 310 mg or less, 300 mg or less, 290 mg or less, 280 mg or less, 270 mg or less, 260 mg or less, 250 mg or less, 240 mg or less, 230 mg or less, 220 mg or less, 210 mg or less, 200 mg or less, 190 mg or less, 180 mg or less, 170 mg or less, 160 mg or less, 150 mg or less, 140 mg or less, 130 mg or less, 120 mg or less, 110 mg or less, 100 mg or less, 90 mg or less, 80 mg or less, 70 mg or less, 60 mg or less, 50 mg or less, 40 mg or less, 30 mg or less, 20 mg or less,10 mg or less, 5 mg or less, or 1 mg or less. In some embodiments, the amount of a bacterial degradation portion in an oral drug dosage form is approximately any one of 1 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 35 mg, 40 mg, 45 mg, 50 mg, 55 mg, 60 mg, 65 mg, 70 mg, 75 mg, 80 mg, 85 mg, 90 mg, 95 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg, 400 mg, 410 mg, 420 mg, 430 mg, 440 mg, 450 mg, 460 mg, 470 mg, 480 mg, 490 mg or 500 mg.

[0217] In some embodiments, the bacterial degradation element is configured to erode during (including within) a predetermined period after exposure to a body fluid, such as after Petition 870250088298, dated 09 / 29 / 2025, pp. 139 / 266 123 / 181 Erosion, such as the substantially complete erosion, of a pH-based enteric element or a layer thereof and / or of an erodible retardant element or a layer thereof. In some embodiments, the bacterial degradation element erodes, such as substantially eroding, to expose another component of an oral drug dosage form, over a period of about 1 minute to about 7 hours. In some embodiments, the bacterial degradation element erodes, such as substantially eroding, another component of an oral drug dosage form, over a period of at least about 5 minutes, such as at least about any of 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, or 7 hours.The synchronicity of erosion of the bacterial degradation element, or a layer thereof, can be based on several factors, including composition (e.g., type and / or quantity of a bacterial degradation portion) and thickness.

[0218] The bacterial degradation element can be formed using numerous materials with varying shapes and sizes. In some embodiments, the bacterial degradation element is a layer of a bacterial degradation material. In some embodiments, the bacterial degradation elements are configured to have surfaces, such as a surface exposed to a body fluid during the administration of the oral drug dosage form to a human subject, with a predetermined shape and surface area. For example, in some embodiments, the bacterial degradation element has an upper surface and a lower surface, where the upper surface is exposed to a body fluid before the lower surface. In some embodiments, the bacterial degradation element Petition 870250088298, dated 09 / 29 / 2025, pp. 140 / 266 124 / 181 Bacterial degradation is a layer with an upper surface and a lower surface. In some embodiments, the upper surface of the bacterial degradation element is not flat, for example, it comprises certain features that extend beyond a top surface plane or a surface tolerance limit (as measured between two parallel planes). In some embodiments, the upper surface of the bacterial degradation element, or at least a part thereof, is flat or lies within a surface tolerance limit.

[0219] In some embodiments, the bacterial degradation element surrounds the drug component. In these embodiments, there may be no additional material between the bacterial degradation element and the drug component, for example, the presence of an erodible retarding element.

[0220] The surfaces of a bacterial degradation element, such as a bacterial degradation element layer, based on the surface exposed to a body fluid after administration, can have any shape. In some embodiments, the surface has the shape of a capsule, circle, oval, projectile shape, arrowhead shape, triangle, arched triangle, square, arched square, rectangle, arched rectangle, rhombus, pentagon, hexagon, octagon, crescent moon, almond, or a combination thereof.

[0221] In some embodiments, the surface of a bacterial degradation element, such as a layer of bacterial degradation element, has a surface area of ​​about 10 mm2 to about 400 mm2, such as any of about 20 mm2 to about 200 mm2, about 20 mm2 to about 100 mm2, about 20 mm2 to about 60 mm2, about 30 mm2 to about 50 mm2. In some embodiments, the surface of a bacterial degradation element has a surface area of ​​at least about 20 mm2, such Petition 870250088298, dated 09 / 29 / 2025, pp. 141 / 266 125 / 181 as at least approximately any of 22 mm2, 24 mm2, mm2, 28 mm2, 30 mm2, 32 mm2, 33 mm2, 34 mm2, 36 mm2, 38 mm2, mm2, 42 mm2, 44 mm2, 46 mm2, 48 mm2, 50 mm2, 52 mm2, 54 mm2, mm2, 58 mm2, 60 mm2, 65 mm2, 70 mm2, 80 mm2, 85 mm2, 90 mm2, mm2, 100 mm2, 110 mm2, 120 mm2, 130 mm2, 140 mm2, 150 mm2, 160 mm2, 170 mm2, 180 mm2, 190 mm2, 200 mm2, 225 mm2, 250 mm2, 275 mm2, 300 mm2, 325 mm2, 350 mm2, 375 mm2or 400 mm2.In some embodiments, the surface area of ​​a bacterial degradation element is less than about 400 mm², such as less than about any of the following: 400 mm², 375 mm², 350 mm², 325 mm², 300 mm², 275 mm², 250 mm², 225 mm², 200 mm², 190 mm², 180 mm², 170 mm², 160 mm², 150 mm², 140 mm², 130 mm², 120 mm², 110 mm², 100 mm², 95 mm², 90 mm², 85 mm², 80 mm², 75 mm², 70 mm², 65 mm², 60 mm², 58 mm², 56 mm², 54 mm², 52 mm². 50 mm2, 48 mm2, 46 mm2, 44 mm2, 42 mm2, 40 mm2, 38 mm2, 36 mm2, 34 mm2, 32 mm2, 30 mm2, 28 mm2, 26 mm2, 24 mm2, 22 mm2or 20 mm2.In some embodiments, the surface area of ​​a bacterial degradation element is approximately any one of 20 mm², 21 mm², 22 mm², 23 mm², 24 mm², 25 mm², 26 mm², 27 mm², 28 mm², 29 mm², 30 mm², 31 mm², 32 mm², 33 mm², 34 mm², mm², 36 mm², 37 mm², 38 mm², 39 mm², 40 mm², 41 mm², 42 mm², mm², 44 mm², 45 mm², 46 mm², 47 mm², 48 mm², 49 mm², 50 mm², mm², 52 mm², 53 mm², 54 mm², 55 mm², 56 mm², 57 mm², 58 mm² mm2, mm2, 60 mm2, 65 mm2, 70 mm2, 80 mm2, 85 mm2, 90 mm2, 95 mm2,. 100 mm2, 110 mm2, 120 mm2, 130 mm2, 140 mm2, 150 mm2, 160 mm2, 170 mm2, 180 mm2, 190 mm2, 200 mm2, 225 mm2, 250 mm2, 275 mm2, 300 mm2, 325 mm2, 350 mm2, 375 mm2or 400 mm2.

[0222] In some embodiments, the surface area of ​​a bacterial degradation element exposed to a body fluid is consistent throughout the thickness of the degradation element. Petition 870250088298, dated 09 / 29 / 2025, pp. 142 / 266 126 / 181 bacterial, for example, as a bacterial degradation element erodes, the surface exposed to body fluid has the same surface area. In some embodiments, the surface area of ​​a bacterial degradation element exposed to body fluid is different at two or more points, for example, as a bacterial degradation element erodes, the surface exposed to body fluid changes, such as increasing and / or decreasing the surface area during the erosion of the bacterial degradation element. In some embodiments, the shape of the surface of a bacterial degradation element exposed to body fluid is consistent throughout the thickness of the bacterial degradation element. In some embodiments, the shape of the surface of a bacterial degradation element exposed to body fluid is different at two or more points.

[0223] In some embodiments, the surface of a bacterial degradation element, such as a bacterial degradation element layer, has a maximum transverse dimension of about 5 mm to about 20 mm, such as any of about 5 mm to about 15 mm, about 6 mm to about 13 mm or about 7 mm to about 11 mm. In some embodiments, the surface of a bacterial degradation element has a maximum transverse dimension of at least about 5 mm, such as at least about any of 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm or 20 mm. In some embodiments, the surface of a bacterial degradation element has a maximum transverse dimension smaller than about 20 mm, such as smaller than about any of 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, or 5 mm.In some embodiments, the surface of a bacterial degradation element has a maximum transverse dimension of approximately any one of 5 mm, 6 mm, Petition 870250088298, dated 09 / 29 / 2025, pp. 143 / 266 127 / 181 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm or 20 mm.

[0224] In some embodiments, the surface of a bacterial degradation element, such as a bacterial degradation element layer, has a transverse dimension perpendicular to the maximum transverse dimension of about 1 mm to about 15 mm, such as any of about 2 mm to about 10 mm, about 2 mm to about 6 mm, or about 1 mm to about 5 mm. In some embodiments, the surface of a bacterial degradation element has a transverse dimension perpendicular to the maximum transverse dimension of at least about 1 mm, such as at least about any of 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, or 15 mm.In some embodiments, the surface of a bacterial degradation element has a transverse dimension perpendicular to the maximum transverse dimension that is less than about 15 mm, such as less than about any of 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, 5 mm, 4 mm, 3 mm, 2 mm, or 1 mm. In some embodiments, the surface of a bacterial degradation element has a transverse dimension perpendicular to the maximum transverse dimension that is about any of 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, or 15 mm.

[0225] In some embodiments, the bacterial degradation element layer has a thickness of about 0.1 mm to about 5 mm, such as any of about 0.2 mm to about 2 mm, about 0.5 mm to about 1.5 mm or about 0.8 mm to about 1.4 mm. In some embodiments, the bacterial degradation element layer has a thickness of at least about 0.1 mm, such as at least about any of 0.2 mm, 0.3 mm, Petition 870250088298, dated 09 / 29 / 2025, pp. 144 / 266 128 / 181 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1.1mm, 1.2mm, 1.3mm, 1.4mm, 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2.0mm, 2.2mm, 2.4mm, 2.6mm, 2.8mm, 3.0mm, 3.2mm, 3.4mm, 3.6mm, 3.8 mm, 4.0 mm, 4.2 mm, 4.4 mm, 4.6 mm, 4.8 mm, or 5 mm. In some embodiments, the bacterial degradation element layer has a thickness less than about 5 mm, such as less than about any of 4.8 mm, 4.6 mm, 4.4 mm, 4.2 mm, 4.0mm, 3.8mm, 3.6mm, 3.4mm, 3.2mm, 3.0mm, 2.8mm, 2.6mm, 2.4mm, 2.2mm, 2.0mm, 1.9mm, 1.8mm, 1.7mm, 1.6mm, 1.5mm, 1.4mm, 1.3mm, 1.2mm, 1.1mm, 1.0mm, 0.9mm, 0.8mm, 0.7mm, 0.6 mm, 0.5 mm, 0.4 mm, 0.3 mm, 0.2 mm, or 0.1 mm. In some embodiments, the bacterial degradation element layer has a thickness of approximately any one of 0.1 mm, 0.2 mm, 0.3 mm, 0.4mm, 0.5mm, 0.6mm, 0.7mm, 0.8mm, 0.9mm, 1.1mm, 1.2mm, 1.3mm, 1.4mm, 1.5mm, 1.6mm, 1.7mm, 1.8mm, 1.9mm, 2.0mm, 2.2mm, 2.4mm, 2.6mm, 2.8mm, 3.0mm, 3.2mm, 3.4mm, 3.6mm, 3.8mm, 4.0mm, 4.2mm, 4.4mm, 4.6mm, 4.8mm or 5mm.

[0226] In some embodiments, the bacterial degradation element layer comprises an upper surface and a lower surface, wherein the thickness, as measured between the upper surface and the lower surface, is substantially consistent, such as within a range of 20% of an average thickness.

[0227] In some embodiments, the bacterial degradation element, such as a bacterial degradation element layer, comprises a thermoplastic material, such as a thermoplastic polymer. In some embodiments, the bacterial degradation element, such as a bacterial degradation element layer, comprises a material comprising any one or more of a matrix material, a plasticizer or other additive, for example, Petition 870250088298, dated 09 / 29 / 2025, pp. 145 / 266 129 / 181 a filler, a binder, a lubricant, a glide and a disintegrant.

[0228] In some embodiments, the bacterial degradation element comprises one or more of the following: stearic acid, medium-chain triglycerides, glyceryl distearate, propylene glycol monolaurate, propylene glycol caprylate, polyoxyl-6 oleoyl glycerides, PEG-6 stearate, PEG-32 stearate, polyoxyl-6 linoleoyl glycerides, polyoxyl-32 lauroyl glycerides, polyoxyl-8 caprylocaproyl glycerides, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan oleate, glyceryl monolinoleate, copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, crospovidone, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, hydroxypropylmethylcellulose phthalate, methylcellulose, methacrylic acid copolymer, poly(methacrylic acid-ethyl acrylate), poly(butyl methacrylate-(2-dimethylaminoethyl)-methyl methacrylate-co-methacrylate),poly(dimethylaminoethyl methacrylate-methacrylic esters), poly(ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate-co-chloride), poly(methyl acrylate-methyl methacrylate-methacrylic acid), poly(methacrylic acid-methyl methacrylate), poly(methacrylic acid-ethyl acrylate), poly(methacrylic acid-methyl methacrylate), polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate E copolymer, hydroxypropylmethylcellulose acetate succinate or hypromellose acetate succinate, methacrylic ester copolymer, methacrylate copolymer ammonium alkyl, ethylcellulose, polyvinyl acetate and polyvinylpyrrolidone, polyvinyl acetal diethyl aminolactate, polyvinyl acetal diethyl amino lactate, maltitol, lactose monohydrate, xylitol,isomalt, sucrose, glucose, dextran 70, maltose, glycerides of, Petition 870250088298, dated 09 / 29 / 2025, pp. 146 / 266 130 / 181 lauroyl polyoxyl-32, caprylocaproyl polyoxyl-8 glycerides, castor oil polyoxyl (35), vitamin E succinate, polyethylene glycol, hydrogenated castor oil, PEG-40, glyceryl monolinoleate or glyceryl dibehenate. 4. Enclosures

[0229] In certain aspects, an oral drug dosage form comprising a shell is provided in this document.

[0230] In some embodiments, the shell comprises an insulating material impermeable to body fluids, such as gastrointestinal fluid. In some embodiments, the shell comprises an insulating material impermeable to certain body fluids, such as stomach fluid. In some embodiments, the shell comprises an insulating material impermeable to body fluids at a certain pH, for example, an insulating material impermeable to body fluids at a pH less than about 7, such as less than about any of 7.5, 8 or 8.5 (for example, the shell does not erode until subjected to a pH greater than about 7, such as greater than about any of 7.5, 8 or 8.5).In some embodiments, the shell comprises an insulating material that is non-erodible, for example, it does not erode substantially during administration to a human subject. In some embodiments, the shell comprises an insulating material that is non-erodible in certain body fluids, such as gastric fluid.

[0231] In some embodiments, the shell comprises an insulating material that is an erodible material with a pH-based erosion and / or erosion rate that allows complete release of a drug component from an oral drug dosage form prior to exposure of a drug component to body fluids due to shell erosion. Petition 870250088298, dated 09 / 29 / 2025, pp. 147 / 266 131 / 181

[0232] In some embodiments, the sheath comprises an insulating material with selective permeability. For example, in some embodiments, the sheath is permeable to a body fluid and impermeable to a drug.

[0233] The shells provided in this document are configured to have surfaces, such as an outward-facing surface exposed to a body fluid during administration of the oral drug dosage form to a human subject. In some embodiments, the shell is configured to control the exposure of another component of an oral drug dosage form (e.g., a pH-based enteric element and an erodible retardant element) to a body fluid, so as to direct the erosion thereof. In some embodiments, the outer surface of the shell is not flat, for example, it comprises certain features that extend beyond a surface plane or surface tolerance limit (as measured between two parallel planes), such as to reduce the adhesion of the shell, or a part thereof, to an internal part of the human subject's body.In some embodiments, the outer surface of the enclosure, or at least a part thereof, is flat or lies within a surface tolerance limit.

[0234] The surfaces of the shell, based on the surfaces exposed to a body fluid, can have any shape. In some embodiments, the surface of a shell, based on the surface exposed to a body fluid, has the shape of a capsule, cylinder, elliptical cylinder, circle, oval, projectile shape, arrowhead shape, triangle, arched triangle, square, arched square, rectangle, arched rectangle, rhombus, pentagon, hexagon, octagon, crescent moon, almond, or a combination thereof. In some embodiments, the shell forms a ring shape, in which other components of Petition 870250088298, dated 09 / 29 / 2025, pp. 148 / 266 132 / 181 an oral drug dosage form are contained within the ring format (e.g., a drug component, a pH-based enteric element, and an erodible retardant element).

[0235] In some embodiments, the casing has a maximum transverse dimension of about 5 mm to about 20 mm, such as any of about 5 mm to about 15 mm, about 6 mm to about 13 mm or about 7 mm to about 11 mm. In some embodiments, the casing has a maximum transverse dimension of at least about 5 mm, such as at least about any of 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm or 20 mm. In some embodiments, the casing has a maximum transverse dimension smaller than about 20 mm, such as smaller than about any one of 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm, or 5 mm. In some embodiments, the casing has a maximum transverse dimension of about any one of 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, or 20 mm.In some embodiments, the maximum transverse dimension is measured along the surface of an oral medication dosage form.

[0236] In some embodiments, the casing has a transverse dimension perpendicular to a maximum transverse dimension of about 5 mm to about 20 mm, such as any of about 5 mm to about 15 mm, about 6 mm to about 13 mm or about 7 mm to about 11 mm. In some embodiments, the casing has a transverse dimension perpendicular to a maximum transverse dimension of at least about 5 mm, such as at least about any of 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm or Petition 870250088298, dated 09 / 29 / 2025, pp. 149 / 266 133 / 181 mm. In some embodiments, the casing has a transverse dimension perpendicular to a maximum transverse dimension smaller than about 20 mm, such as smaller than about any of 19 mm, 18 mm, 17 mm, 16 mm, 15 mm, 14 mm, 13 mm, 12 mm, 11 mm, 10 mm, 9 mm, 8 mm, 7 mm, 6 mm or 5 mm. In some embodiments, the casing has a transverse dimension perpendicular to a maximum transverse dimension of about any of 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm or 20 mm. In some embodiments, the transverse dimension perpendicular to a maximum transverse dimension is measured along the surface of an oral drug dosage form.

[0237] In some embodiments, the shell is configured to have a thickness that prevents and / or inhibits the exposure of components of an oral drug dosage form, or part thereof, to a body fluid. In some embodiments, the shell has a thickness, as measured from an outer surface of an oral drug dosage form relative to another component thereof, of about 0.3 mm to about 3 mm, such as any of about 0.3 mm to about 1 mm, about 0.4 mm to about 2 mm, or about 0.5 mm to about 1.5 mm. In some embodiments, the casing has a thickness of at least about 0.3 mm, such as at least about any one of 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 2.0 mm, 2.2 mm, 2.4 mm, 2.6 mm, 2.8 mm or 3.0 mm.In some embodiments, the casing has a thickness less than about 3 mm, such as less than about any of 2.8 mm, 2.6 mm, 2.4 mm, 2.2 mm, 2.0 mm, 1.9 mm, 1.8 mm, 1.7 mm, 1.6 mm, 1.5 mm, 1.4 mm, 1.3 mm, 1.2 mm, 1.1 mm, 1.0 mm, 0.9 mm, 0.8 mm, 0.7 mm, 0.6 mm, 0.5 mm, 0.4 mm or 0.3 mm. Petition 870250088298, dated 09 / 29 / 2025, pp. 150 / 266 134 / 181 In some embodiments, the casing has a thickness of approximately any one of 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1.8 mm, 1.9 mm, 2.0 mm, 2.2 mm, 2.4 mm, 2.6 mm, 2.8 mm, 3.0 mm.

[0238] In some embodiments, the casing comprises a thermoplastic material, such as a thermoplastic polymer. In some embodiments, the casing comprises a material comprising any one or more of a matrix material, a plasticizer and another additive, for example, a filler, a binder, a lubricant, a slip agent and a disintegrant.

[0239] In some embodiments, the matrix material comprises one or more of the following: copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, crospovidone, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, hydroxypropylmethylcellulose phthalate, methylcellulose, methacrylic acid copolymer, poly(methacrylic acid-ethyl co-acrylate), poly(butyl methacrylate-(2-dimethylaminoethyl)-methyl methacrylate co-methacrylate), poly(dimethylaminoethyl methacrylate-methacrylic esters), poly(ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate co-chloride), poly(methyl acrylate-methyl methacrylate-methacrylic acid co-methacrylate), poly(methacrylic acid-co-methyl methacrylate), poly(ethyl methacrylic acid-co-acrylate), poly(methyl methacrylic acid-co-acrylate), polyethylene oxide, polyethylene glycol,polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate E copolymer, hydroxypropylmethylcellulose acetate succinate or hypromellose acetate succinate, methacrylic ester copolymer, copolymer, Petition 870250088298, dated 09 / 29 / 2025, pp. 151 / 266 135 / 181 of ammonium alkyl methacrylate, ethylcellulose, polyvinyl acetate and polyvinylpyrrolidone, polyvinyl acetal diethyl amino lactate, polyvinyl acetal diethyl amino lactate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose, dextran 70 or maltose.

[0240] In some embodiments, the plasticizer is any one or more of the following: triethyl citrate, vitamin E succinate, polyethylene glycol, acetylated triethyl citrate, tributyl citrate, tributyl o-acetylcitrate, polyoxyl 15 hydroxystearate, PEG-40 hydrogenated castor oil, polyoxyl 35 castor oil, dibutyl sebacate, diethyl phthalate, glycerin, methyl 4-hydroxybenzoate, castor oil, oleic acid, triacetin, polyalkylene glycol, stearic acid, palmitic acid, malic acid, polyethylene glycol, PEG-32 lauroyl glycerides, poloxamer 188, poloxamer 407, acetyltributyl citrate, D-sorbitol, propylene glycol, diethyl phthalate, citric acid, behenate glyceryl, D-mannitol, polysorbate, sorbitan monostearate, sorbitan monooleate or polyoxyl 40 stearate.

[0241] In some embodiments, the other additive is any one or more of the following: acacia, alginate, alginic acid, aluminum acetate, butylparaben, butylated hydroxytoluene, citric acid, calcium carbonate, candelilla wax, croscarmellose sodium, confectioners' sugar, colloidal silicon dioxide, cellulose, simple or anhydrous calcium phosphate, carnauba wax, corn starch, calcium carboxymethylcellulose, calcium disodium ethylenediaminetetraacetic acid, dehydrated calcium hydrogen phosphate, cetylpyridinium chloride, dibasic calcium phosphate, tribasic calcium phosphate, dibasic calcium phosphate, disodium hydrogen phosphate, dimethicone, erythrosine sodium, ethylenediaminetetraacetic acid, gelatin, glyceryl monooleate, iron oxide, ferric oxide, yellow iron oxide, red iron oxide, lactose (aqueous, anhydrous, monohydrate or spray-dried), microcrystalline cellulose, magnesium carbonate, magnesium oxide, methylparaben, polysorbate 80,propylparaben, potassium bicarbonate, potassium sorbate, potato starch, Petition 870250088298, dated 09 / 29 / 2025, pp. 152 / 266 136 / 181 phosphoric acid, polyoxyethylene stearate (40), sodium starch glycolate, pregelatinized starch, croscarmellose sodium, sodium lauryl sulfate, starch, silicon dioxide, sodium benzoate, sucrose, sorbic acid, sodium carbonate, sodium saccharin, sodium alginate, silica gel, sorbitan monooleate, sodium chloride, sodium metabisulfite, sodium citrate dehydrate, sodium starch, sodium carboxymethylcellulose, succinic acid, sodium propionate, titanium dioxide or talc. 5. Additional components

[0242] In some embodiments, the oral drug dosage form comprises one or more additional components.

[0243] In some embodiments, the oral drug dosage form comprises an excipient.

[0244] In some embodiments, the excipient is mixed into the drug component. In some embodiments, the excipient is mixed into an erodible retardant element. In some embodiments, the excipient is mixed into a bacterial degradation element. In some embodiments, the excipient is mixed into an excipient component, wherein the excipient component comprises an erodible material. In some embodiments, the excipient comprises one or more of an absorption enhancer, a pH-reducing agent, or a disintegrant. In some embodiments, the excipient is selected based on whether the oral drug dosage form, or a drug contained therein, is intended for local or systemic release. For example, absorption enhancers may have particular utility in an oral drug dosage form formulated for systemic release.In some embodiments, the oral drug dosage form comprises a drug intended for systemic release and a drug intended for local release (as disposed of in separate compartments of the oral drug dosage form), wherein... Petition 870250088298, dated 09 / 29 / 2025, pp. 153 / 266 The 137 / 181 oral drug dosage form is configured so that an absorption-enhancing excipient is released to aid in the systemic uptake of the drug intended for systemic release.

[0245] In some embodiments, the oral drug dosage form comprises an adjuvant. For example, certain drugs, such as biological agents, for example, peptides, and / or nucleic acids, may benefit from an adjuvant to help protect the drug once released in the gastrointestinal tract, thus providing improved uptake. In some embodiments, the adjuvant is a protease scavenger and / or a protease inhibitor. In some embodiments, the protease scavenger or protease inhibitor is mixed with the retarding component, or a part thereof (such as an erodible retarding component). In some embodiments, the protease scavenger or protease inhibitor is mixed into the erodible material of the erodible retarding element.

[0246] In some embodiments, the additional component comprises, such as, an outer coating. In some embodiments, the outer coating is a flavor coating. In some embodiments, the outer coating is a sugar coating. In some embodiments, the outer coating is a cosmetic coating. In some embodiments, the outer coating is a colored coating. In some embodiments, the outer coating is a film coating. In some embodiments, the outer coating is a polymeric coating. In some embodiments, the additional component is a label, such as a company name, abbreviation or logo, a drug label or drug name, such as a trade name of the drug and / or chemical name or abbreviation of the drug, a quantity or potency of the drug, an identification barcode or any combination thereof. Petition 870250088298, dated 09 / 29 / 2025, pp. 154 / 266 138 / 181 C. Release profiles of oral drug dosage forms and their components.

[0247] The oral drug dosage forms described in this document are configured to release a drug to a desired location in an individual's colon. In some embodiments, the oral drug dosage form is configured to release the drug into, near, or downstream of any of the cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, or sigmoid colon. In some embodiments, at least about 95% (such as at least about any of 96%, 97%, 98%, 99%, or 100%) of the drug in the oral drug dosage form is released from the oral drug dosage form into the individual's colon. In some embodiments, less than about 2% (such as less than about any of 1.9%, 1.8%, 1.7%, 1.6%, 1.5%, 1.4%, 1.3%, 1.2%, 1.1%, 1.0%, 0.9%, 0.8%, 0.7%, 0.6%, 0.5%, 0.4%, 0.3%, 0.2%, or 0.1%) of the drug in the oral dosage form is released from the oral dosage form outside the individual's colon.In some embodiments, substantially all, including all, of the drug in the oral dosage form is released from the oral dosage form into the individual's colon.

[0248] In some embodiments, the oral drug dosage form is configured to release the drug into, near, or downstream of the individual's ileum. In some embodiments, the oral drug dosage form is configured to release the drug into, near, or downstream of the individual's large intestine (colon), or a portion thereof. In some embodiments, the oral drug dosage form is configured to release the drug into, near, or downstream of the cecum, ascending colon, transverse colon, descending colon, and / or sigmoid colon. In some embodiments, the oral drug dosage form is configured to release the drug into, near, or downstream of the rectum. Petition 870250088298, dated 09 / 29 / 2025, pp. 155 / 266 139 / 181

[0249] At the desired site in the colon for drug release, the oral drug dosage forms described in this document can be configured to release a drug according to any release profile. In some embodiments, the oral drug dosage form is configured to release a drug according to a controlled-release profile. In some embodiments, the controlled-release profile is an immediate-release profile. For example, as described in this document, the drug component releases a drug contained therein in about 1 hour or less, such as about any of 50 minutes or less, 40 minutes or less, 30 minutes or less, 25 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 9 minutes or less, 8 minutes or less, 7 minutes or less, 6 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, or 1 minute or less.In some embodiments, the controlled-release profile is a prolonged-release profile. For example, as described in this document, the drug component releases a drug for at least about 1 hour, such as at least about 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, or 7 hours. In some embodiments, the drug component of an oral drug dosage form is configured to release a drug from the oral drug dosage form for at least about 1 hour, such as at least about any one of 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, or 8 hours.

[0250] In some embodiments, the oral drug dosage form is configured to provide a drug release profile comprising a zero-order release profile, first-order release profile, delayed-release profile, pulsed-release profile, Petition 870250088298, dated 09 / 29 / 2025, pp. 156 / 266 140 / 181 iterative pulsed release profile, immediate release profile or prolonged release profile or a combination thereof.

[0251] As described in this document, in some embodiments, the oral drug dosage form may comprise another drug (including two or more, three or more, four or more, or five or more). In these embodiments, the other drug(s) may be released according to any desired release profile. In some embodiments, the desired drug release profile of another drug comprises a zero-order release profile, a first-order release profile, a delayed-release profile, a pulsed-release profile, an iterative pulsed-release profile, an immediate-release profile, or a prolonged-release profile, or a combination thereof.

[0252] In some embodiments, drug release is based, at least in part, on an in vitro dissolution study, as described in U.S. Patent No. 10,350,822, which is incorporated herein in its entirety. In some embodiments, drug release is based, at least in part, on an in vivo dissolution study, as described in U.S. Patent Publication No. 2021 / 0196638 A, which is incorporated herein in its entirety. III. Commercial lot

[0253] In some aspects, a commercial batch of at least about 100 oral drug dosage forms described in this document is provided in this document. In some embodiments, the commercial batch comprises at least about any one of 250, 500, 750, 1,000, 2,500, 5,000, 7,500, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000, 70,000, 80,000, 90,000 or 100,000 of the oral drug dosage forms described in this document.

[0254] In some forms, the commercial lot has a standard deviation of about 0.1 or less, such as 0.05 or less, for one or Petition 870250088298, dated 09 / 29 / 2025, pp. 157 / 266 141 / 181 plus one of the following: a quantity of a drug and / or agent, such as a bacterial degradation portion, in the form of an oral drug dosage form; a weight of the oral drug dosage form; a maximum transverse dimension of the oral drug dosage form; a transverse dimension perpendicular to the maximum transverse dimension of the oral drug dosage form; and a layer thickness. IV. Methods for manufacturing and designing dosage forms of oral drugs described in this document.

[0255] In some aspects, methods for manufacturing an oral drug dosage form described in this document are provided in this document. In some embodiments, the manufacturing method comprises a three-dimensional (3D) printing technique for forming at least one of the components, or a part thereof, of the oral drug dosage forms described in this document. In some embodiments, the 3D printing techniques allow precise control of drug release to be achieved through fine-tuning of different parameters, such as geometry, fill percentages, or composition.

[0256] In some embodiments, a three-dimensional (3D) printing method of an oral drug dosage form is provided, the method comprising dispensing materials according to a layer-by-layer model of the oral drug dosage form (such as based on the thickness of the material deposited by a pass of a print head) to print the oral drug dosage form, wherein each layer of the layer-by-layer model is printed by dispensing, as required, a layer of: (a) a shell material to form any part of a shell in the layer; (b) a drug component material to form any part of a drug component in the layer; Petition 870250088298, dated 09 / 29 / 2025, pp. 158 / 266 142 / 181 (c) a pH-based enteric element material to form any part of a pH-based enteric element in the layer; (d) an erodible retardant element material to form any part of an erodible retardant element in the layer; (e) a bacterial degradation element material to form any part of a bacterial degradation element in the layer; and (f) an excipient component material to form any part of an excipient component in the layer.

[0257] In some embodiments, the oral drug dosage form comprises (a) a drug component comprising an erodible material mixed with a drug; and (b) a pH-based enteric element (not mixed with the drug) comprising an erodible material configured to erode at or above a predetermined pH value, the 3D printing method comprising dispensing materials according to a layer-by-layer model of the oral drug dosage form (such as based on the thickness of the material deposited by a pass of a print head) to print the oral drug dosage form, wherein each layer of the layer-by-layer model is printed by dispensing, as required, a layer of: (a) a drug component material to form any part of the drug component in the layer; and (b) the pH-based enteric element material to form any part of a pH-based enteric element in the layer.In some embodiments, the method additionally comprises the generation of a layer-by-layer model of the oral drug dosage form.

[0258] In some embodiments, the oral drug dosage form comprises (a) a drug component comprising an erodible material mixed with a drug; (b) an enteric element Petition 870250088298, dated 09 / 29 / 2025, pp. 159 / 266 143 / 181 pH-based (not mixed with the drug) comprising an erodible material configured to erode at or above a predetermined pH value; and (c) an erodible retarding element comprising an erodible material not mixed with the drug, the 3D printing method comprising dispensing materials according to a layer-by-layer model of the oral drug dosage form (such as based on the thickness of the material deposited by a pass of a print head) to print the oral drug dosage form, wherein each layer of the layer-by-layer model is printed by dispensing, as required, a layer of: (a) a drug component material to form any part of the drug component in the layer; (b) a pH-based enteric element material to form any part of the pH-based enteric element in the layer;and (c) an erodible retarding element material to form any part of the erodible retarding element in the layer. In some embodiments, the method further comprises generating a layer-by-layer model of the oral drug dosage form.

[0259] In some embodiments, the oral drug dosage form comprises (a) a drug component comprising an erodible material mixed with a drug; (b) a pH-based enteric element (not mixed with the drug) comprising an erodible material configured to erode at or above a predetermined pH value; and (c) a bacterial degradation element comprising a bacterial degradation moiety, the 3D printing method comprising dispensing materials according to a layer-by-layer model of the oral drug dosage form (such as based on the thickness of the material deposited by a pass of a print head) to print the oral drug dosage form, wherein each layer of the model is layer by layer. Petition 870250088298, dated 09 / 29 / 2025, pp. 160 / 266 Layer 144 / 181 is printed by dispensing, as needed, a layer of: (a) a drug component material to form any part of the drug component in the layer; (b) a pH-based enteric element material to form any part of the pH-based enteric element in the layer; and (c) a bacterial degradation element material to form any part of the bacterial degradation element in the layer. In some embodiments, the method further comprises generating the layer-by-layer model of the oral drug dosage form.

[0260] In some embodiments, the oral drug dosage form comprises (a) a drug component comprising an erodible material mixed with a drug; (b) a pH-based enteric element (not mixed with the drug) comprising an erodible material configured to erode at or above a predetermined pH value; (c) an erodible retarding element comprising an erodible material not mixed with the drug;and (d) a bacterial degradation element comprising a bacterial degradation portion, the 3D printing method comprising dispensing materials according to a layer-by-layer model of the oral drug dosage form (such as based on the thickness of the material deposited by a pass of a print head) to print the oral drug dosage form, wherein each layer of the layer-by-layer model is printed by dispensing, as needed, a layer of: (a) a drug component material to form any part of the drug component in the layer; (b) a pH-based enteric element material to form any part of the pH-based enteric element in the layer; (c) an erodible retardant element material to form any part of the erodible retardant element in the layer; and a bacterial degradation element material to form any part of the; Petition 870250088298, dated 09 / 29 / 2025, pp. 161 / 266 145 / 181 bacterial degradation element in the layer. In some embodiments, the method further comprises the generation of a layer-by-layer model of the oral drug dosage form.

[0261] In some embodiments, the oral drug dosage form comprises (a) a drug component comprising an erodible material mixed with a drug; (b) a pH-based enteric element (not mixed with the drug) comprising an erodible material configured to erode at or above a predetermined pH value; and (c) an excipient component comprising an excipient, the 3D printing method comprising dispensing materials according to a layer-by-layer model of the oral drug dosage form (such as based on the thickness of the material deposited by a pass of a print head) to print the oral drug dosage form, wherein each layer of the layer-by-layer model is printed by dispensing, as required, a layer of: (a) a drug component material to form any part of the drug component in the layer;(b) a pH-based enteric element material to form any part of the pH-based enteric element in the layer; and (c) an excipient component material to form any part of the excipient component in the layer. In some embodiments, the method further comprises generating a layer-by-layer model of the oral drug dosage form.

[0262] In some embodiments, the oral drug dosage form comprises (a) a drug component comprising an erodible material mixed with a drug; (b) a pH-based enteric element (not mixed with the drug) comprising an erodible material configured to erode at or above a predetermined pH value; (c) an erodible retardant element comprising Petition 870250088298, dated 09 / 29 / 2025, pp. 162 / 266 146 / 181 an erodible material not mixed with the drug; and (d) an excipient component comprising an excipient, the 3D printing method comprising dispensing materials according to a layer-by-layer model of the oral drug dosage form (such as based on the thickness of the material deposited by a pass of a print head) to print the oral drug dosage form, wherein each layer of the layer-by-layer model is printed by dispensing, as required, a layer of: (a) a drug component material to form any part of the drug component in the layer; (b) a pH-based enteric element material to form any part of the pH-based enteric element in the layer; (c) an erodible retarding element material to form any part of the erodible retarding element in the layer; and (d) an excipient component material to form any part of the excipient component in the layer.In some embodiments, the method additionally comprises the generation of a layer-by-layer model of the oral drug dosage form.

[0263] In some embodiments, the oral drug dosage form comprises (a) a drug component comprising an erodible material mixed with a drug; (b) a pH-based enteric element (not mixed with the drug) comprising an erodible material configured to erode at or above a predetermined pH value; (c) an erodible retardant element comprising an erodible material not mixed with the drug; (d) a bacterial degradation element comprising a bacterial degradation moiety; and (e) an excipient component comprising an excipient, the 3D printing method comprising dispensing materials according to a layer-by-layer model of the form Petition 870250088298, dated 09 / 29 / 2025, pp. 163 / 266 147 / 181 of oral drug dosage form (such as based on the thickness of the material deposited by one pass of a print head) to print the oral drug dosage form, wherein each layer of the layer-by-layer pattern is printed by dispensing, as required, a layer of: (a) a drug component material to form any part of the drug component in the layer; (b) a pH-based enteric element material to form any part of the pH-based enteric element in the layer; (c) an erodible retardant element material to form any part of the erodible retardant element in the layer; (d) a bacterial degradation element material to form any part of the bacterial degradation element in the layer; and (e) an excipient component material to form any part of the excipient component in the layer.In some embodiments, the method additionally comprises the generation of a layer-by-layer model of the oral drug dosage form.

[0264] For any of the above embodiments, the oral drug dosage form may further comprise a shell not mixed with the drug. For embodiments in which the oral drug dosage form comprises a shell, the method further comprises dispensing materials according to a layer-by-layer pattern of the oral drug dosage form (such as based on the thickness of the material deposited by a pass of a printing head) to print the oral drug dosage form, wherein each layer of the layer-by-layer pattern is printed by dispensing, as needed, a layer of shell material to form any part of the shell in the layer. Petition 870250088298, dated 09 / 29 / 2025, pp. 164 / 266 148 / 181

[0265] As used in this document, “printing,” “three-dimensional printing,” “3D printing,” “additive manufacturing,” or equivalents thereof, refer to a process that produces three-dimensional objects, such as oral drug dosage forms, layer by layer, using digital designs. The basic three-dimensional printing process has been described in U.S. Patents Nos. 5,204,055; 5,260,009; 5,340,656; 5,387,380; 5,503,785; and 5,633,021. Additional U.S. patents and patent applications relating to three-dimensional printing include: U.S. Patents Nos. 5,490,962; 5,518,690; 5,869,170; 6,530,958; 6,280,771; 6,514,518; 6,471,992; 8,828,411; U.S. Publications Nos. 2002 / 0015728; 2002 / 0106412; 2003 / 0143268; 2003 / 0198677; 2004 / 0005360. The contents of the aforementioned U.S. patents and patent applications are incorporated herein in their entirety.In some embodiments, an additive manufacturing technique is used to produce the oral drug dosage forms described in this document. In some embodiments, a layer-by-layer technique is used to produce the oral drug dosage forms described in this document. Because 3D printing can handle a variety of pharmaceutical materials and control both composition and architecture locally, 3D printing is well suited for manufacturing oral drug dosage forms with complex geometry and compositions according to the present invention.

[0266] In some embodiments, layer, when used in reference to, for example, a drug component layer or a delay component layer (e.g., a pH-based enteric element layer and / or an erodible delay element layer), refers to the configuration of a component of the oral drug dosage form and may comprise a plurality of printed layers of the same material. In some embodiments, the Petition 870250088298, dated 09 / 29 / 2025, pp. 165 / 266 The 149 / 181 layer has a predetermined infill density, such as a three-dimensional printed infill density. In some embodiments, the layer, such as the drug component layer, comprises a plurality of printed layers ranging from about 5 printed layers to about 2500 printed layers, such as from any of about 10 printed layers to about 2500 printed layers, about 25 printed layers to about 100 printed layers, about 50 printed layers to about 200 printed layers, about 100 printed layers to about 200 printed layers, about 150 printed layers to about 250 printed layers, about 200 printed layers to about 250 printed layers, about 500 printed layers to about 1000 printed layers, or about 2000 printed layers to about 2400 printed layers.In some embodiments, the thickness of a printed layer is no more than about 5 mm, as well as no more than about any one of 4 mm, 3 mm, 2 mm, 1 mm, 0.9 mm, 0.8 mm, 0.7 mm, 0.6 mm, 0.5 mm, 0.4 mm, 0.3 mm, 0.2 mm, 0.1 mm, 0.09 mm, 0.08 mm, 0.07 mm, 0.06 mm, 0.05 mm, 0.04 mm, 0.03 mm, 0.02 mm or 0.01 mm. In some embodiments, the thickness of a printed layer is approximately any one of 5 mm, 4 mm, 3 mm, 2 mm, 1 mm, 0.9 mm, 0.8 mm, 0.7 mm, 0.6 mm, 0.5 mm, 0.4 mm, 0.3 mm, 0.2 mm, 0.1 mm, 0.09 mm, 0.08 mm, 0.07 mm, 0.06 mm, 0.05 mm, 0.04 mm, 0.03 mm, 0.02 mm, or 0.01 mm.

[0267] Different 3D printing methods have been developed for manufacturing in terms of raw materials, equipment, and solidification. These 3D printing methods include binder deposition (see Gibson et al., Additive Manufacturing Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing, 2nd ed. Springer, New York, 2015; Katstra et al., Oral dosage forms fabricated Petition 870250088298, dated 09 / 29 / 2025, pp. 166 / 266 150 / 181 by three dimensional printing, J Control Release, 66, 2000; Katstra et al., Fabrication of complex oral delivery forms by three dimensional printing, Dissertation in Materials Science and Engineering, Massachusetts Institute of Technology, 2001; Lipson et al., Fabricated: The New World of 3D printing, John Wiley & Sons, Inc., 2013; Jonathan, Karim 3D printing in pharmaceutics: a new tool for designing customized drug delivery systems, Int J Pharm, 499, 2016), jateamento de material (vide Jonathan, Karim, 3D printing in pharmaceutics: a new tool for designing customized drug delivery systems, Int J Pharm, 499, 2016), extrusão (vide Gibson et al., Aditive Manufacturing Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing. 2 ed. Springer, Nova Iorque, 2015), e fotopolimerização (vide Melchels etal., A review on stereolithography and its application in biomedical engineering. Biomaterials, 31, 2010).

[0268] In some embodiments, the oral drug dosage forms described in this document are 3D printed using an extrusion method. In some embodiments, the 3D printing method comprises the use of a twin-screw extrusion method. In an extrusion process, material is extruded from robotically driven print heads through print nozzles. Unlike binder deposition, which requires a powder bed, extrusion methods can print on any substrate. A variety of materials can be extruded for three-dimensional printing, including thermoplastic materials described in this document, pastes and colloidal suspensions, silicones, and other semi-solids. One extrusion printing method is extrusion-fused-deposition (EDD), which uses material extruded from a print head to print layers of material in order to form the components of the oral drug dosage form. Another common type of printing by Petition 870250088298, dated 09 / 29 / 2025, pp. 167 / 266 151 / 181 Extrusion is fused deposition modeling, which uses solid polymer filaments for printing. In fused deposition modeling, a gear system drives the filament through a set of heated nozzles for extrusion (see Gibson et al., Additive Manufacturing Technologies: 3D Printing, Rapid Prototyping, and Direct Digital Manufacturing, 2nd ed. Springer, New York, 2015).

[0269] In some embodiments, 3D printing is performed by semi-solid extrusion, such as semi-solid extrusion of a material comprising a biological drug, for example, a polypeptide or a nucleic acid. In some embodiments, 3D printing is performed by MED and semi-solid extrusion, for example, semi-solid extrusion to produce a drug component mixed with a biological drug and MED to produce other components. In some embodiments, 3D printing is performed by MED to produce a lag or shell component, and then 3D printing is performed by semi-solid extrusion to produce a drug component mixed with a biological drug at lower temperatures than MED. In some embodiments, the drug in the drug component can be kept stable by means of semi-solid extrusion.

[0270] In some embodiments, 3D printing is performed by extrusion-fused-to-deposition (EDD). In some embodiments, the EFD technique involves preparing a material to be dispensed, such as preparing a powder in a hot melt extruder, and then feeding the material into an EFD print head. The EFD print head then dispenses the material to form the oral drug dosage form in an additive manner (layer-by-layer deposition). In some embodiments, each material of the oral drug dosage form, such as the extended-release drug component, the element Petition 870250088298, dated 09 / 29 / 2025, pp. 168 / 266 152 / 181 of delay and the envelope, is dispensed from a different MED printhead. In some embodiments, the MED printhead dispenses the material according to instructions compiled in one or more G-code files. Exemplary MED techniques are described in, for example, WO2018 / 210183, WO2019 / 137333, WO2018137686 and U.S. Patent No. 10,201,503, each of which is incorporated herein in its entirety.

[0271] In some embodiments, the fused deposition (FDD) 3D printing technique comprises: (a) preparing each component material by melting and extruding the component material; and (b) printing an oral drug dosage form using a layer-by-layer technique. In some embodiments, the fused deposition (FDD) 3D printing technique further comprises preparing a print head for printing. In some embodiments, the preparation of the drug component material comprises melting and extruding the drug component material. In some embodiments, the preparation of the drug component material comprises mixing the ingredients of the drug component material, such as any thermoformable components and a drug. In some embodiments, the preparation of the drug component material comprises weighing each ingredient thereof, mixing the ingredients, and melting and extruding the drug component material.In some embodiments, the preparation of the casing material comprises melting and extruding the casing material. In some embodiments, the preparation of the casing material comprises mixing the ingredients of the casing material, such as any thermoformable components thereof. In some embodiments, the preparation of the casing material comprises weighing each ingredient thereof, mixing the ingredients, and melting and extruding the material. Petition 870250088298, dated 09 / 29 / 2025, pp. 169 / 266 153 / 181 casing. In some embodiments, the preparation of the pH-based enteric element material comprises melting and extruding the pH-based enteric element material. In some embodiments, the preparation of the pH-based enteric element material comprises mixing the ingredients of the pH-based enteric element material, such as any thermoformable components thereof. In some embodiments, the preparation of the pH-based enteric element material comprises weighing each ingredient thereof, mixing the ingredients, and melting and extruding the pH-based enteric element material. In some embodiments, the preparation of the erodible retardant element material comprises melting and extruding the erodible retardant element material. In some embodiments, the preparation of the erodible retardant material comprises mixing the ingredients of the erodible retardant material, such as any thermoformable components thereof.In some embodiments, the preparation of the erodible retardant material comprises weighing each ingredient thereof, mixing the ingredients, and melting and extruding the erodible retardant material. In some embodiments, the preparation of the bacterial degradation element material comprises melting and extruding the bacterial degradation element material. In some embodiments, the preparation of the bacterial degradation element material comprises mixing the ingredients of the bacterial degradation element material, such as any thermoformable components and a bacterial degradation portion. In some embodiments, the preparation of the bacterial degradation element material comprises weighing each ingredient thereof, mixing the ingredients, and melting and extruding the bacterial degradation element material. In some embodiments, the preparation of the excipient component material comprises melting and extruding the excipient component material.In some sports, preparation. Petition 870250088298, dated 09 / 29 / 2025, pp. 170 / 266 154 / 181 of the excipient component material comprises mixing the ingredients of the excipient component material, such as any thermoformable components and a portion of excipient. In some embodiments, the preparation of the excipient component material comprises weighing each ingredient thereof, mixing the ingredients, and melting and extruding the excipient component material.

[0272] In some embodiments, printhead preparation for printing comprises loading the formed component material, such as a drug component material, into the printhead. In some embodiments, printhead preparation for printing comprises adjusting the printhead temperature. In some embodiments, printhead preparation for printing comprises setting and applying the feed pressure to the printhead. In some embodiments, the application of the feed pressure is completed after the printhead temperature reaches a predetermined level. In some embodiments, the printing of the oral drug dosage form is performed layer by layer (e.g., additive manufacturing).In some embodiments, the method comprises using a separate printhead for each component material (for example, a first printhead to dispense a drug component material, a second printhead to dispense a shell material, a third printhead to dispense a pH-based enteric element material, and a fourth printhead to dispense an erodible retardant element material). In some embodiments, the manufacturing method is designed and carried out based on a desired total number of an oral drug dosage form that will be produced in a production batch. For example, in some embodiments, a smaller production batch (such as less than 1,000 drug dosage forms). Petition 870250088298, dated 09 / 29 / 2025, pp. 171 / 266 155 / 181 oral for product development or a clinical trial) is desired and the manufacturing method comprises preparing each component material (such as by weighing the ingredients of a component material and forming the component material by mixing the ingredients and hot melt extrusion), and then printing each oral drug dosage form layer by layer (e.g., additive manufacturing). In some embodiments, a larger production batch (such as a commercial mass production batch greater than 1.The production of 000 units of an oral drug dosage form is desired, and the manufacturing method comprises preparing each component material (such as by weighing the ingredients of a component material and forming the component material by mixing the ingredients and hot melt extrusion, wherein the hot melt extrusion is performed using a twin-screw extruder), and then printing each oral drug dosage form layer by layer (e.g., additive manufacturing). In some embodiments, the component material is formed using, at least partially, a twin-screw extruder. In some embodiments, the larger production batch comprises the distribution of the component material from the twin-screw extruder to each print head by means of a flow distribution module. In some embodiments, the larger production batch is performed through the cooperation of multiple modules.For example, in some embodiments, the manufacturing method comprises the use of a system comprising a material supply module to receive a set of component materials for printing; a flow distribution module comprising a flow distribution plate, wherein the material supply module is configured to transport a single flow corresponding to the set of component materials for printing to the flow distribution plate; wherein the flow distribution plate. Petition 870250088298, dated 09 / 29 / 2025, pp. 172 / 266 156 / 181 comprises a plurality of channels to divide a single stream into a plurality of streams; a plurality of nozzles; and one or more controllers to control the plurality of nozzles in order to dispense the plurality of streams based on a plurality of nozzle-specific parameters. In some embodiments, the system further comprises a printing platform configured to receive the dispensed plurality of streams, wherein the printing platform is configured to move in order to form a batch of the pharmaceutical product. In some embodiments, the system comprises a plurality of printing platforms.

[0273] In some modalities, 3D printing is performed by fused deposition modeling (FDM). In some modalities, three-dimensional printing is performed by extrusion-fused deposition or hot extrusion coupled with a 3D printing technique, such as FDM. In some modalities, 3D printing is performed by non-filamentary FDM. In some modalities, 3D printing is performed by inkjet printing. In some modalities, 3D printing is performed by selective laser sintering (SLS). In some modalities, 3D printing is performed by stereolithography (SLA or SL).In some modalities, 3D printing is performed by PolyJet, MultiJet Printing System (MJP), Perfactory, Solid Object Ultraviolet Laser Printer, Bioplotter, 3D Bioprinting, Rapid Freeze Prototyping, Benchtop System, Selective Deposition Lamination (SDL), Laminated Object Fabrication (LOM), Ultrasonic Consolidation, ColorJet Printing (CJP), EOSINT Systems, Laser Network Forming (LENS) and Aerosol Jet System, Electron Beam Fusion (EBM), Laser CUSING®, Selective Laser Melting (SLM), Phenix PX™ Series, Microsintering, Digital Part Materialization (DPM) or VX System. Petition 870250088298, dated 09 / 29 / 2025, pp. 173 / 266 157 / 181

[0274] In some embodiments, the 3D printing methods described in this document comprise a continuous feed method. In some embodiments, the 3D printing methods described in this document comprise a batch feed method.

[0275] The instructions for the 3D printing method of a drug dosage form described in this document can be generated in several ways, including direct coding, derivation from a solid CAD model, or other means specific to the 3D printing machine's computer interface and application software. These instructions may include information on the number and spatial arrangement of droplets, as well as general 3D printing parameters such as droplet spacing in each linear dimension (X, Y, Z) and the volume or mass of fluid per droplet. For a given set of materials, these parameters can be adjusted to refine the quality of the created structure. The overall resolution of the created structure is a function of the powder particle size, fluid droplet size, printing parameters, and material properties.

[0276] In some embodiments, one or more components of the oral drug dosage form are created separately, such as printed separately, and subsequently assembled to form the oral drug dosage form. In some embodiments, all components of the oral drug dosage form are created in a single method, such as printed in a single method, without the need for subsequent assembly. For example, in some embodiments, the oral drug dosage form is produced using a layer-by-layer 3D printing technique.

[0277] The oral drug dosage forms and their components described in this application may be printed to scale. Petition 870250088298, dated 09 / 29 / 2025, pp. 174 / 266 158 / 181 commercial. For example, in some embodiments, the methods described in this document can be used to 3D print 10,000 to 100,000 units of an oral drug dosage form per hour. In some embodiments, the methods described in this document can be used to 3D print 10,000 to 100,000 oral drug dosage forms per hour. In some embodiments, the methods described in this document can be used to 3D print 10,000 to 100,000 dosage units per hour. In some embodiments, the methods described in this document can be used to 3D print 10,000 to 100,000 dosage units per hour.

[0278] The 3D printing methods described in this document encompass printing the materials in any order that allows the production of the oral drug dosage form or components thereof.

[0279] In some embodiments, the method for 3D printing comprises designing the oral drug dosage form, or a component thereof, wholly or partially, into a computational system. In some embodiments, the method comprises inputting parameters of the drug release profile at the desired location and / or of the oral drug dosage form into the computational system. In some embodiments, the method comprises providing one or more parameters to be printed, for example, layer surface area, thickness, drug mass portion, erosion rate. In some embodiments, the method comprises providing the desired drug release profile. In some embodiments, the methods comprise creating a virtual image of the item to be printed. In some embodiments, the method comprises creating a computational model containing the predetermined parameters. In some embodiments, the method comprises creating a computational model containing the predetermined parameters. Petition 870250088298, dated 09 / 29 / 2025, pp. 175 / 266 159 / 181 but embodiments, the method comprises feeding predetermined parameters to a 3D printer and printing the item according to such predetermined parameters. In some embodiments, the method comprises creating a 3D drawing of the item to be printed based on the predetermined parameters, wherein the 3D drawing is created in a computer system. In some embodiments, the method comprises converting, such as slicing, a 3D drawing into 3D printing code, for example, G-code. In some embodiments, the method comprises using the computer system to execute 3D printing code, thus printing according to the methods described in this document.

[0280] In some respects, the methods provided in this document comprise one or more packaging steps. In some embodiments, the packaging step comprises packaging each individual dosage form in a discreet container, such as laminated film and pharmaceutical packaging bags. In some embodiments, the packaging step comprises packaging a quantity of packaged dosage forms in a box.

[0281] In some embodiments, the method additionally comprises one or more quality control steps during the process. For example, in some embodiments, after the manufacture of the dosage form, the quality control step during the process comprises one or more of the following: evaluating a dosage form for appearance or a feature thereof, evaluating the dosage form for weight, and evaluating the dosage form for dimensions. In some embodiments, to pass the quality control step during the process, the evaluated characteristic must be within a predetermined limit. In some embodiments, after each dosage form is packaged, the quality control step during the process comprises evaluating the sealing of each dosage form, by Petition 870250088298, dated 09 / 29 / 2025, pp. 176 / 266 160 / 181 example, regarding airtightness and / or the amount of filling. In some methods, after packaging in the box, the quality control step during the process includes confirming the amount of filling in the box.

[0282] In some embodiments, the design methods provided in this document comprise the use of one or more tracking tracks, so that external imaging techniques, for example, x-ray imaging, can be used to assess the state (such as whether erosion / release of the oral drug dosage form has not yet occurred, is undergoing erosion / release of the oral drug dosage form, or completion of erosion / release of the oral drug dosage form) of one or more components of an oral drug dosage form taught in this document in relation to the location of the oral drug dosage form in the individual to whom it was administered. For example, such tracking capabilities then allow confirmation that one or more components of an oral drug dosage form are behaving as desired, such as the release of a drug from a drug component occurring at a desired location in an individual's gastrointestinal tract.This additionally allows for methods comprising adjusting the design of an oral drug dosage form to provide the desired results. For example, if it is found that a drug component is eroding and releasing the drug at a site before the desired one (e.g., upstream of the desired site in the gastrointestinal tract), then one or more aspects of the delaying component can be adjusted, such as by altering a composition or thickness of a material thereof.

[0283] In some embodiments, a method is provided for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, in Petition 870250088298, dated 09 / 29 / 2025, pp. 177 / 266 161 / 181 that the oral drug dosage form comprises: a drug component comprising: a first erodible material mixed with a drug and a first erodible tracking strip; and a shell comprising a second tracking strip; a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value, wherein the pH-based enteric element comprises a third erodible tracking strip;and an erodible retardant element comprising a second erodible material, wherein the erodible retardant element comprises a fourth erodible tracking strip, wherein the pH-based enteric element, alone or in combination with the casing, prevents erosion of the erodible retardant element, and wherein the erodible retardant element, alone or in combination with the casing, prevents erosion of the drug component, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over a period of time to obtain the location of the oral drug dosage form and a state of the first erodible tracking strip, the second erodible tracking strip, the third erodible tracking strip and the fourth tracking strip;and (c) adjust the drug component and / or the delay component and / or the shell, or part thereof, based on the location and state of the first erodible tracking band, the second erodible tracking band, the third erodible tracking band, and the fourth tracking band, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

[0284] In some embodiments, the adjustment of the retarding component comprises adjusting the enteric element on a pH basis by altering Petition 870250088298, dated 09 / 29 / 2025, pp. 178 / 266 162 / 181 one or more of the following: the composition, the surface area exposed to body fluid after administration, or the thickness of the pH-based enteric element. In some embodiments, the adjustment of the delay component comprises adjusting the erodible delay element by altering one or more of the following: the composition, the surface area exposed to body fluid after administration, or the thickness of the erodible delay element.

[0285] In some embodiments, a method is provided in this document for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, wherein the oral drug dosage form comprises: a drug component comprising: a first erodible material mixed with a drug, and a first erodible tracking strip; and an envelope; a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value;and an erodible retardant element comprising a second erodible material, wherein the pH-based enteric element, alone or in combination with the shell, prevents erosion of the erodible retardant element, and wherein the erodible retardant element, alone or in combination with the shell, prevents erosion of the drug component, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over a period of time to obtain the location of the oral drug dosage form and a state of the first erodible tracking band; and (c) adjusting the drug component and / or the retardant component and / or the shell, or part thereof, based on the location and state of the first erodible tracking band, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual. Petition 870250088298, dated 09 / 29 / 2025, pp. 179 / 266 163 / 181

[0286] In some embodiments, the first erodible material mixed with the drug and the first erodible tracking strip are not in direct contact with each other. In some embodiments, the envelope comprises a second tracking strip, wherein the second tracking strip is configured to be imaged in order to obtain a state of the second tracking strip. In some embodiments, the adjustment is based on the location and state of the first erodible tracking strip and / or the second tracking strip. In some embodiments, the pH-based enteric element comprises a third tracking strip, wherein the third tracking strip is configured to be imaged in order to obtain a state of the third erodible tracking strip.In some embodiments, the adjustment is based on the location and state of the first erodible tracking strip, and / or the second tracking strip, and / or the third erodible tracking strip. In some embodiments, the erodible delay element comprises a fourth tracking strip, and in which the fourth tracking strip is configured to be imaged in order to obtain a state of the fourth erodible tracking strip. In some embodiments, the adjustment is based on the location and state of the first erodible tracking strip, and / or the second tracking strip, and / or the third erodible tracking strip, and / or the fourth erodible tracking strip.

[0287] In some modalities, image acquisition provides a location of the oral drug dosage form when the first erodible tracking band begins to erode. In some modalities, image acquisition provides a location of the oral drug dosage form when the first erodible tracking band has completely eroded. In some modalities, the adjustment comprises adjusting the Petition 870250088298, dated 09 / 29 / 2025, pp. 180 / 266 164 / 181 delay component, or part thereof, to increase the delay in drug release from the oral drug dosage form, based on the location and state of the first erodible tracking strip showing earlier release relative to the desired release. In some embodiments, the adjustment comprises adjusting the delay component, or part thereof, to reduce the delay in drug release from the oral drug dosage form based on the location and state of the first erodible tracking strip showing later release relative to the desired release.

[0288] In some embodiments, the first tracking strip comprises barium sulfate. In some embodiments, imaging comprises x-ray imaging. In some embodiments, the method further comprises obtaining one or more pharmacokinetic (PK) parameters associated with the drug after administration of the oral drug dosage form to an individual. In some embodiments, the method further comprises identifying a relationship between one or more PK parameters and the location and state information of the first tracking strip. In some embodiments, the method further comprises adjusting the drug component and / or the delay component, or part thereof, based on the relationship between one or more PK parameters and the location and state information of the first tracking strip. In some embodiments, imaging does not involve a magnetism-based technique or an invasive imaging technique.

[0289] In some embodiments, a method is provided in this document for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, wherein the oral drug dosage form comprises: a drug component comprising a first erodible material mixed with a drug; a shell; and a component of Petition 870250088298, dated 09 / 29 / 2025, pp. 181 / 266 165 / 181 retardation not mixed with the drug, the retardation component comprising: an enteric pH-based element configured to erode at or above a predetermined pH value; and an erodible retardation element comprising a second erodible material, wherein the enteric pH-based element prevents erosion of the erodible retardation element, and wherein the erodible retardation element prevents erosion of the drug component, wherein the oral drug dosage form comprises at least one tracking strip positioned on a component thereof, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over a period of time to obtain a location of the oral drug dosage form and a state of at least one tracking strip;and (c) adjust the drug component and / or delay component and / or coating, or part thereof, based on the location and state of at least one tracking strip, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

[0290] In some embodiments, one of the tracking bands is located on, or near, the drug component. In some embodiments, the tracking bands are located on the shell. In some embodiments, one of the tracking bands is located on the pH-based enteric element. In some embodiments, one of the tracking bands is located on the erodible retardant element. In some embodiments, at least one of the tracking bands is erodible.

[0291] In some embodiments, a method is provided in this document for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, wherein the oral drug dosage form comprises: Petition 870250088298, dated 09 / 29 / 2025, pp. 182 / 266 166 / 181 a drug component comprising a first erodible material mixed with a drug; and a retardation component not mixed with the drug, the retardation component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value; and an erodible retardation element comprising a second erodible material, wherein the pH-based enteric element prevents erosion of the erodible retardation element, and wherein the erodible retardation element prevents erosion of the drug component, wherein the oral drug dosage form comprises at least one tracking strip positioned on a component thereof, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over a period of time to obtain a location of the oral drug dosage form and a state of at least one tracking strip;and (c) adjust the drug component and / or delay component, or part thereof, based on the location and status of at least one tracking band, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

[0292] In some embodiments, one of the tracking bands is located on, or near, the drug component. In some embodiments, one of the tracking bands is located on the pH-based enteric element. In some embodiments, one of the tracking bands is located on the erodible retardant element. In some embodiments, at least one of the tracking bands is erodible.

[0293] In some embodiments, a method is provided for designing and / or adjusting an oral drug dosage form described in this document configured to release a drug at a desired site. Petition 870250088298, dated 09 / 29 / 2025, pp. 183 / 266 167 / 181 in an individual's colon. In some embodiments, the adjustment comprises adjusting the delay component, or part thereof, to increase the delay in drug release from the oral drug dosage form. As described in this document, "adjustment" may refer to making a change in a parameter that, for example, influences the rate at which a component erodes from an oral drug dosage form. For example, in some embodiments, "adjustment" may refer to making a change in one or more of the following: thickness, drug mass portion, density, composition, surface area exposed to a body fluid, or erosion rate of a material. In some embodiments, the adjustment is based on data obtained from the study of an oral drug dosage form described in this document, such as in vitro and / or in vivo studies, for example, cumulative dissolution profiles or PK studies.Techniques for adjusting features of an oral drug dosage form to increase or decrease the delay in drug release are known in the art, and include, for example, adjustments in thickness, surface area, and material properties. Adjustment techniques are described in U.S. Patent No. 10,350,822, which is incorporated herein by reference in its entirety.

[0294] In some embodiments, the design method further comprises obtaining, such as by measuring, one or more pharmacokinetic (PK) parameters associated with the drug after administration of the oral drug dosage form to an individual. PK parameters are well known in the art and include, for example, Tdet, Tmax, Cmax, and AUC. Design methods involving PK parameters are described in U.S. Patent No. 2021 / 0196638 A, which is incorporated herein in its entirety. Petition 870250088298, dated 09 / 29 / 2025, pp. 184 / 266 168 / 181 V. Treatment and / or release methods

[0295] In some respects, methods are provided in this document for treating a condition comprising administering (orally) an oral drug dosage form described in this document to an individual. In some respects, methods are provided in this document for providing local release of a drug in the colon of an individual, the method comprising administering (orally) to the individual an oral drug dosage form described in this document, for example, to treat an individual suffering from a gastrointestinal disorder. In some respects, methods are provided in this document for providing systemic release of a drug to an individual, the method comprising administering (orally) to the individual an oral drug dosage form described in this document, for example, to release a biological agent such as a peptide or nucleic acid.

[0296] The oral drug dosage forms described in this document may comprise a variety of agents and therefore the methods of use may be useful for treating a wide variety of conditions.In some modalities, the condition is selected from the group consisting of a gastrointestinal disorder, central nervous system (CNS) disorder, cardiovascular disease, hypertension, atherosclerosis, angina, arterial obstruction, peripheral arterial disease, myocardial pathology, arrhythmia, acute myocardial infarction, angina, cardiomyopathy, congestive heart failure, coronary artery disease (CAD), carotid artery disease, endocarditis, hypercholesterolemia, hyperlipidemia, peripheral arterial disease (PAD), genitourinary disorders; erectile dysfunction, urinary tract diseases, benign prostatic hypertrophy (BPH), renal tubular acidosis, diabetic nephropathy, glomerulonephritis, glomerulosclerosis, urinary tract infection, fecal incontinence, eye disease, glaucoma, blepharitis, ocular hypertension, retinopathy. Petition 870250088298, dated 09 / 29 / 2025, pp. 185 / 266 169 / 181 conjunctivitis, scleritis, retinitis, keratitis, corneal ulcer, iritis, chorioretinal inflammation, macular edema, xerophthalmia, pulmonary disease, asthma, pulmonary hypertension, acute respiratory distress syndrome, COPD, emphysema, pneumonia, tuberculosis, bronchitis, acute bronchitis, bronchiectasis, bronchiolitis, bronchopulmonary dysplasia, byssinosis, coccidioidomycosis (Cocci), cystic fibrosis, influenza, lung cancer, mesothelioma, metabolic disease, hypercalciuria, hyperglycemia, hyperinsulinemic hypoglycemia, hyperinsulinism, hyperlysinuria, and hypoglycemia. In some modalities, the gastrointestinal disorder is selected from the group consisting of irritable bowel disease (IBD), irritable bowel syndrome (IBS), constipation, diarrhea, infection, and carcinoma. In some forms, IBD is associated with Crohn's disease or ulcerative colitis. In some forms, the carcinoma is colon cancer or colorectal cancer.In some modalities, the CNS disorder is selected from the group that consists of neurogenic pain, stroke, dementia, Alzheimer's disease, Parkinson's disease, neuronal degeneration, meningitis, spinal cord injury, cerebral vasospasm, and amyotrophic lateral sclerosis.

[0297] In some embodiments, a method is provided for delivering local release of a drug into the colon of an individual, the method comprising administering to the individual an oral drug dosage form described in this document, wherein the individual is suffering from a gastrointestinal disorder. In some embodiments, the gastrointestinal disorder is selected from the group consisting of irritable bowel disease (IBD), irritable bowel syndrome (IBS), constipation, diarrhea, infection, and carcinoma. In some embodiments, IBD is associated with Crohn's disease or ulcerative colitis. In some embodiments, carcinoma is colon cancer or colorectal cancer. In some embodiments, the oral drug dosage form comprises an anti-inflammatory agent, a non-anti-inflammatory agent Petition 870250088298, dated 09 / 29 / 2025, pp. 186 / 266 170 / 181 steroidal or steroid. In some embodiments, the drug component comprises tofacitinib, for example, tofacitinib citrate.

[0298] In some embodiments, a method is provided for treating ulcerative colitis, the method comprising administering to a human subject an oral drug dosage form described in this document, wherein the oral drug dosage form comprises a JAK inhibitor. In some embodiments, the JAK inhibitor comprises tofacitinib. In some embodiments, the oral drug dosage form comprises about 11 mg or less of tofacitinib. In some embodiments, the oral drug dosage form comprises about 5.5 mg or less of tofacitinib. In some embodiments, the method comprises administering the oral drug dosage form once daily.

[0299] In some embodiments, a method of treating ulcerative colitis is provided, the method comprising administering to a human subject an oral drug dosage form described in this document, wherein the drug component comprises a JAK inhibitor. In some embodiments, the JAK inhibitor comprises tofacitinib. In some embodiments, the oral drug dosage form comprises about 5.5 mg or less of tofacitinib. In some embodiments, the method comprises administering the oral drug dosage form once daily.

[0300] In some embodiments, a method of treatment for ulcerative colitis is provided, the method comprising administering to a human subject an oral drug dosage form described in this document, wherein the drug component comprises 5.5 mg of tofacitinib and the method comprises administering the oral drug dosage form once daily. Petition 870250088298, dated 09 / 29 / 2025, pp. 187 / 266 171 / 181

[0301] In some embodiments, a method is provided for delivering systemic release of a drug to an individual, the method comprising administering (orally) to the individual an oral drug dosage form described in this document, wherein the individual is suffering from a central nervous system (CNS) disorder, cardiovascular disease, hypertension, atherosclerosis, angina, arterial obstruction, peripheral arterial disease, myocardial pathology, arrhythmia, acute myocardial infarction, angina, cardiomyopathy, congestive heart failure, coronary artery disease (CAD), carotid artery disease, endocarditis, hypercholesterolemia, hyperlipidemia, peripheral arterial disease (PAD), genitourinary disorders; Erectile dysfunction, urinary tract diseases, benign prostatic hyperplasia (BPH), renal tubular acidosis, diabetic nephropathy, glomerulonephritis, glomerulosclerosis, urinary tract infection, fecal incontinence, eye disease, glaucoma, blepharitis.Ocular hypertension, retinopathy, conjunctivitis, scleritis, retinitis, keratitis, corneal ulcer, iritis, chorioretinal inflammation, macular edema, xerophthalmia, pulmonary disease, asthma, pulmonary hypertension, acute respiratory distress syndrome, COPD, emphysema, pneumonia, tuberculosis, bronchitis, acute bronchitis, bronchiectasis, bronchiolitis, bronchopulmonary dysplasia, byssinosis, coccidioidomycosis (Cocci), cystic fibrosis, influenza, lung cancer, mesothelioma, metabolic disease, hypercalciuria, hyperglycemia, hyperinsulinemic hypoglycemia, hyperinsulinism, hyperlysinuria, or hypoglycemia. In some embodiments, the oral drug dosage form comprises a biological agent, such as a peptide, an antibody, or a nucleic acid (e.g., RNA). In some embodiments, the RNA is selected from the group consisting of transfer RNA (tRNA), ribosomal RNA (rRNA), or messenger RNA (mRNA).

[0302] People skilled in the art will recognize that various embodiments are possible within the scope and spirit of the invention. Petition 870250088298, dated 09 / 29 / 2025, pp. 188 / 266 172 / 181 of this application. The invention is further illustrated by the examples below, which should not be interpreted as limiting the invention in scope or spirit to the specific procedures described therein. EXAMPLES Example 1

[0303] This example demonstrates the desi...

Claims

1. An oral drug dosage form configured to release a drug at a desired location in an individual's colon, characterized in that it comprises: a drug component comprising an erodible material mixed with the drug; and a delay component not mixed with the drug, wherein the delay component is configured to prevent the release of the drug from the drug component until the oral drug dosage form reaches the individual's colon after administration, and wherein the delay component comprises: a pH-based enteric element comprising an erodible material configured to erode at or above a predetermined pH value.

2. Oral drug dosage form according to claim 1, characterized in that the delay component further comprises an erodible delay element, and wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible delay element.

3. Oral drug dosage form according to claim 2, characterized in that the pH-based enteric element at least partially prevents erosion of the erodible retarding element, and the erodible retarding element at least partially prevents erosion of the drug component.

4. Oral drug dosage form, according to any one of claims 1 to 3, characterized in that it further comprises a second drug. Petition 870250088298, dated 09 / 29 / 2025, pp. 199 / 266 2 / 28 5. Oral drug dosage form according to claim 4, characterized in that the second drug is mixed with the drug component.

6. Oral drug dosage form according to claim 4, characterized in that it further comprises a second drug component comprising an erodible material mixed with the second drug, wherein the delay component is configured to prevent the release of the second drug from the second drug component until the oral drug dosage form reaches the colon of the individual after administration.

7. Oral drug dosage form according to claim 6, characterized in that the delay component comprises a second erodible delay element, wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible delay element, the erodible delay element erodes before the second drug component, the second drug component erodes before the second erodible delay element, and the second erodible delay element erodes before the drug component.

8. Oral drug dosage form according to claim 7, characterized in that the pH-based enteric element at least partially prevents erosion of the erodible retarding element, the erodible retarding element at least partially prevents erosion of the second drug component, the second drug component at least partially prevents erosion of the second erodible retarding element, and the second erodible retarding element at least partially prevents erosion of the drug component.

9. Oral drug dosage form, according to claim 7 or 8, characterized in that the erodible material of the erodible delay element and the erodible material of the second erodible delay element are the same.

10. Oral drug dosage form, according to claim 7 or 8, characterized in that the erodible material of the erodible delay element and the erodible material of the second erodible delay element are different.

11. Oral drug dosage form, according to any one of claims 2 to 10, characterized in that it further comprises a bacterial degradation portion.

12. Oral drug dosage form, according to claim 11, characterized in that the bacterial degradation portion is mixed with the erodible material of the erodible retardant element.

13. Oral drug dosage form according to claim 11, characterized in that the bacterial degradation portion is mixed with the drug component.

14. Oral drug dosage form, according to any one of claims 11 to 13, characterized in that the delay component further comprises a bacterial degradation element comprising an erodible material mixed with the bacterial degradation portion, wherein the oral drug dosage form is configured such that the pH-based enteric element erodes before the erodible delay element, the erodible delay element erodes before the bacterial degradation element, and the bacterial degradation element erodes before the drug component.

15. Oral drug dosage form according to claim 14, characterized in that the pH-based enteric element at least partially prevents erosion of the erodible retarding element, the erodible retarding element at least partially prevents erosion of the bacterial degradation element, and the bacterial degradation element at least partially prevents erosion of the drug component.

16. Oral drug dosage form, according to any one of claims 11 to 15, characterized in that the bacterial degradation portion is digestible by one or more microorganisms present in the colon of the individual.

17. Oral drug dosage form, according to any one of claims 11 to 16, characterized in that the bacterial degradation moiety comprises one or more saccharides.

18. Oral drug dosage form according to claim 17, characterized in that one or more saccharides comprise any one or more of sucrose, glucose, xylose, fructose, maltose, galactose, pectin, galactomannan, dextran, inulin, chitosan, carrageenan, cellulose acetate propionate (CAP), peptidoglycan, gellan, xanthan gum, lentinan, psyllium polysaccharide, corn bran arabinoxylan, alginate, hyaluronic acid, fucoidan, shellac, agar or maltodextrin.

19. Oral drug dosage form, according to any one of claims 14 to 18, characterized in that the bacterial degradation element is a layer, and in that the layer has a thickness, based on the direction of erosion, of about 0.1 mm to about 5 mm.

20. Oral drug dosage form, according to any one of claims 14 to 19, characterized in that the bacterial degradation element comprises a surface area exposed to gastrointestinal fluid in the individual of about 10 mm2 to about 400 mm2.

21. Oral drug dosage form, according to any one of claims 1 to 20, characterized in that the delay component does not comprise an erodible delay element.

22. Oral drug dosage form according to claim 21, characterized in that the erodible material of the pH-based enteric element comprises one or more of hypromellose acetate succinate, hydroxypropylmethylcellulose phthalate, cellulose acetate propionate (CAP), poly(ethyl methacrylic acid-co-acrylate) or polyvinyl acetate phthalate (PVAP).

23. Oral drug dosage form according to claim 22, characterized in that hypromellose succinate acetate is HPMCAS LG / LF, HPMCAS MG / MF or HPMCAS HG / LF.

24. Oral drug dosage form according to claim 22, characterized in that the hydroxypropylmethylcellulose phthalate is HPMCP HP-50 or HPMCP HP-55.

25. Oral drug dosage form according to claim 22, characterized in that the poly(ethyl methacrylic acid-co-acrylate) is Eudragit L100-55 or Eudragit L100.

26. Oral drug dosage form, according to any one of claims 1 to 25, characterized in that the drug component comprises an upper surface, a lower surface and one or more lateral surfaces, wherein the drug component is incorporated into the delay component such that erosion of the delay component, or an aspect thereof, exposes at least two surfaces of any one of the upper surface, the lower surface or at least one of the one or more lateral surfaces to the gastrointestinal fluid of the individual.

27. Oral drug dosage form according to any one of claims 1 to 26, characterized in that the oral drug dosage form does not comprise a shell. Petition 870250088298, dated 09 / 29 / 2025, pp. 203 / 266 6 / 28 28. Oral drug dosage form, according to any one of claims 1 to 25, characterized in that the oral drug dosage form further comprises a shell not mixed with the drug, wherein the oral drug dosage form is configured such that the shell, or a portion thereof, and the delay element prevent erosion of the drug component.

29. Oral drug dosage form, according to claim 28, characterized in that the direction of erosion of the delay component and / or the drug component occurs based on the configuration of the shell.

30. Oral drug dosage form, according to any one of claims 1 to 29, characterized in that it further comprises a protease scavenger and / or a protease inhibitor.

31. Oral drug dosage form according to claim 30, characterized in that the protease scavenger or protease inhibitor is mixed with the delay component or a part thereof.

32. Oral drug dosage form, according to claim 30 or 31, characterized in that the protease scavenger or protease inhibitor is mixed into the erodible material of the erodible retarding element.

33. Oral drug dosage form, according to any one of claims 1 to 32, characterized in that the oral drug dosage form is configured to release the drug in, near, or downstream of any one of the cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, or sigmoid colon.

34. Oral drug dosage form, according to any one of claims 1 to 33, characterized in that at least about 95% of the drug in the oral drug dosage form is released from the oral drug dosage form into the colon of the individual.

35. Oral drug dosage form, according to any one of claims 1 to 34, characterized in that less than about 2% of the drug in the oral drug dosage form is released from the oral drug dosage form outside the colon of the individual.

36. Oral drug dosage form, according to any one of claims 1 to 35, characterized in that all of the drug in the oral drug dosage form is released from the oral drug dosage form into the colon of the individual.

37. Oral drug dosage form, according to any one of claims 2 to 36, characterized in that the drug component and / or the delay component are in the form of one or more layers.

38. Oral drug dosage form according to claim 37, characterized in that the pH-based enteric element layer comprises an upper surface and a lower surface, wherein the erodible retardant element layer comprises an upper surface and a lower surface, wherein the drug component layer comprises an upper surface and a lower surface, wherein the lower surface of the pH-based enteric element layer is in contact with the upper surface of the erodible retardant element layer, and wherein the lower surface of the erodible retardant element layer is in contact with the upper surface of the drug component layer. Petition 870250088298, dated 09 / 29 / 2025, pp. 205 / 266 8 / 28 39. Oral drug dosage form, according to any one of claims 1 to 38, characterized in that the oral drug dosage form is configured to have more than one compartment, and wherein at least one compartment comprises the drug component and the delay component.

40. Oral drug dosage form, according to any one of claims 1 to 39, characterized in that the pH-based enteric element erodes at or above a pH value of about 5.

5.

41. Oral drug dosage form, according to any one of claims 1 to 40, characterized in that the pH-based enteric element is a layer with a thickness, based on the direction of erosion, of about 0.1 mm to about 5 mm.

42. Oral drug dosage form, according to any one of claims 1 to 41, characterized in that the pH-based enteric element comprises a surface area exposed to gastrointestinal fluid in the individual of about 10 mm2 to about 400 mm2.

43. Oral drug dosage form, according to any one of claims 1 to 42, characterized in that the external surfaces of the oral drug dosage form, before administration to the individual, comprise the pH-based enteric element and, optionally, the shell.

44. Oral drug dosage form, according to any one of claims 1 to 43, characterized in that the pH-based enteric element comprises a thermoformable material.

45. Oral drug dosage form, according to any one of claims 1 to 44, characterized in that the pH-based enteric element comprises one or more of the following: acid Petition 870250088298, dated 09 / 29 / 2025, page. 206 / 266 9 / 28 stearic acid, copovidone, polyvinylpyrrolidone-co-vinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, crospovidone, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, hydroxypropylmethylcellulose phthalate, methylcellulose, methacrylic acid copolymer, poly(methacrylic acid-ethyl acrylate), poly(butyl methacrylate-(2-dimethylaminoethyl)-methyl methacrylate-co-methacrylate), poly(dimethylaminoethyl methacrylate-methacrylic esters), poly(ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate-co-chloride), poly(methyl acrylate-methyl methacrylate-co-methacrylic acid), poly( methacrylate-co-methyl methacrylate),poly(methacrylic acid-ethyl methacrylate), poly(methacrylic acid-methyl methacrylate), polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate E copolymer, hydroxypropylmethylcellulose acetate succinate or hypromellose acetate succinate, methacrylic ester copolymer, ammonium alkyl methacrylate copolymer, ethylcellulose, polyvinyl acetate and polyvinylpyrrolidone, polyvinyl acetal diethyl aminolactate, polyvinyl acetal diethyl aminolactate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose, dextran or maltose.

46. ​​Oral drug dosage form, according to any one of claims 2 to 45, characterized in that the erodible delay element prevents the release of the drug from the drug component for at least about 10 minutes after contact of the erodible delay element with a gastrointestinal fluid in the individual.

47. Oral drug dosage form, according to any one of claims 2 to 46, characterized in that the erodible retarding element is a layer with a thickness, based on the direction of erosion, of about 0.1 mm to about 5 mm.

48. Oral drug dosage form, according to any one of claims 2 to 47, characterized in that the erodible retardant element comprises a surface area exposed to gastrointestinal fluid in the individual of about 10 mm2 to about 400 mm2.

49. Oral drug dosage form, according to any one of claims 2 to 48, characterized in that the erodible retardant element comprises a thermoformable material.

50. Oral drug dosage form, according to any one of claims 2 to 49, characterized in that the erodible retarding element comprises one or more of the following: stearic acid, medium-chain triglycerides, glyceryl distearate, propylene glycol monolaurate, propylene glycol caprylate, polyoxyl-6 oleoyl glycerides, PEG-6 stearate, PEG-32 stearate, polyoxyl-6 linoleoyl glycerides, polyoxyl-32 lauroyl glycerides, polyoxyl-8 caprylocaproyl glycerides, sorbitan monolaurate, sorbitan monopalmitate, sorbitan monostearate, sorbitan oleate, glyceryl monolinoleate, copovidone, polyvinylpyrrolidone-covinyl acetate copolymer of polyvinylpyrrolidone-polyvinyl acetate, crospovidone, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, hydroxypropylmethylcellulose phthalate, methylcellulose, methacrylic acid copolymer, poly(methacrylic acid-ethyl coacrylate),poly(butyl methacrylate-(2-dimethylaminoethyl)-methyl methacrylate), poly(dimethylaminoethyl methacrylate-methacrylic copolymers), poly(ethyl acrylate-methyl methacrylate-trimethylammonioethyl methacrylate chloride), poly(methyl acrylate-methyl methacrylate-methacrylic acid), poly(methacrylic acid-methyl methacrylate), poly(methacrylic acid-ethyl coacrylate), poly(methacrylic acid-methyl methacrylate), polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-alcohol graft copolymer polyvinyl, Kollicoat IR - polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate copolymer E, hydroxypropylmethylcellulose succinate acetate or hypromellose succinate acetate, methacrylic ester copolymer, ammonium alkyl methacrylate copolymer, ethylcellulose,polyvinyl acetate and polyvinylpyrrolidone, polyvinyl acetal diethyl aminolactate, polyvinyl acetal diethyl amino lactate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose, dextran, maltose, lauroyl polyoxyl-32 glycerides, caprylocaproyl polyoxyl-8 glycerides, castor oil polyoxyl (35), vitamin E succinate, polyethylene glycol, PEG-40 hydrogenated castor oil, glyceryl monolinoleate or glyceryl dibehenate.

51. Oral drug dosage form, according to any one of claims 1 to 50, characterized in that the drug component is not in direct contact with the pH-based enteric element.

52. Oral drug dosage form according to any one of claims 1 to 51, characterized in that the drug component is a controlled-release drug component.

53. Oral drug dosage form according to any one of claims 1 to 51, characterized in that the drug component is a sustained-release drug component.

54. Oral drug dosage form according to any one of claims 1 to 51, characterized in that the drug component is an immediate-release drug component. Petition 870250088298, dated 09 / 29 / 2025, pp. 209 / 266 12 / 28 55. Oral drug dosage form, according to any one of claims 1 to 51, characterized in that the drug component is configured to release the drug from the oral drug dosage form for at least about 1 hour.

56. Oral drug dosage form, according to any one of claims 1 to 55, characterized in that the drug component is configured to provide a drug release profile comprising a zero-order release profile, a first-order release profile, a delayed-release profile, a pulsed-release profile, an iterative pulsed-release profile, an immediate-release profile, or a prolonged-release profile, or a combination thereof.

57. Oral drug dosage form, according to any one of claims 1 to 56, characterized in that the drug release is based, at least partially, on an in vitro dissolution study.

58. Oral drug dosage form, according to any one of claims 1 to 57, characterized in that the drug release is based, at least partially, on an in vivo dissolution study.

59. Oral drug dosage form, according to any one of claims 1 to 58, characterized in that the drug component has a drug mass portion (mp) of about 0.05 to about 0.

6.

60. Oral drug dosage form, according to any one of claims 1 to 59, characterized in that the weight ratio between the drug component and the delay component is about 1:10 to 10:

1.

61. Oral drug dosage form, according to any one of claims 1 to 60, characterized in that the drug component is a layer with a thickness, based on the direction of erosion, of about 0.1 mm to 5 mm.

62. Oral drug dosage form, according to any one of claims 1 to 61, characterized in that the drug component comprises a surface area exposed to gastrointestinal fluid in the individual of about 10 mm2 to about 400 mm2.

63. Oral drug dosage form, according to any one of claims 1 to 62, characterized in that the drug component comprises a thermoformable material.

64. Oral drug dosage form, according to any one of claims 1 to 63, characterized in that the drug component comprises one or more of the following: copovidone, polyvinylpyrrolidone-covinyl acetate, polyvinylpyrrolidone-polyvinyl acetate copolymer, polyvinylpyrrolidone, hydroxypropylcellulose, hydroxypropylmethylcellulose or hypromellose, polyethylene oxide, polyethylene glycol, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, polyethylene glycol-polyvinyl alcohol graft copolymer, Kollicoat IR-polyvinyl alcohol, polyvinyl alcohol, aminoalkyl methacrylate E copolymer, hydroxypropylmethylcellulose acetate succinate, hypromellose acetate succinate, hydroxypropylmethylcellulose phthalate, maltitol, lactose monohydrate, xylitol, isomalt, sucrose, glucose or dextran.

65. Oral drug dosage form, according to any one of claims 1 to 64, characterized in that it further comprises one to four additional drug components.

66. Oral drug dosage form, according to any one of claims 1 to 65, characterized in that the drug is an anti-inflammatory agent, non-steroidal anti-inflammatory agent, steroid, immunosuppressant, antibiotic, antineoplastic agent, Petition 870250088298, dated 09 / 29 / 2025, p. 211 / 266 14 / 28 analgesic, anesthetic, anticonvulsant, antidiabetic agent, antihistamine, anti-infective, antineoplastic, antiparkinsonian agent, antirheumatic agent, appetite stimulant, appetite suppressant, blood modifier, bone metabolism modifier, cardiovascular agent, central nervous system depressant, central nervous system stimulant, decongestant, dopamine receptor agonist, electrolyte, gastrointestinal agent, immunomodulator, muscle relaxant, narcotic, parasympathomimetic, sympathomimetic, sedative, hypnotic or vaccine.

67. Oral drug dosage form according to claim 66, characterized in that the anti-inflammatory agent is a JAK inhibitor.

68. Oral drug dosage form according to claim 67, characterized in that the JAK inhibitor is tofacitinib or a pharmaceutically acceptable salt thereof.

69. Oral drug dosage form according to claim 66, characterized in that the anti-inflammatory agent is mesalazine, sulfasalazine or balsalazide.

70. Oral drug dosage form according to claim 66, characterized in that the non-steroidal anti-inflammatory agent is ibuprofen or diclofenac.

71. Oral drug dosage form according to claim 66, characterized in that the steroid is prednisolone, budesonide or fluticasone.

72. Oral drug dosage form according to claim 57, characterized in that the immunosuppressant is azathioprine, cyclosporine or methotrexate.

73. Oral drug dosage form according to claim 66, characterized in that the antineoplastic agent is fluorouracil, methotrexate, dactinomycin, bleomycin, etoposide, taxol, Petition 870250088298, dated 09 / 29 / 2025, page 212 / 266 15 / 28 vincristine, doxorubicin, cisplatin, daunorubicin, etoposide, raltitrexed or oxaliplatin or a combination thereof.

74. Oral drug dosage form, according to any one of claims 1 to 73, characterized in that the oral drug dosage form comprises from about 0.01 mg to about 500 mg of the drug.

75. Oral drug dosage form, according to any one of claims 1 to 74, characterized in that it further comprises an excipient.

76. Oral drug dosage form according to claim 75, characterized in that the excipient comprises one or more of an absorption enhancer, a pH-reducing agent, or a disintegrant.

77. Oral drug dosage form, according to claim 75 or 76, characterized in that the excipient is mixed with the drug component.

78. Oral drug dosage form, according to any one of claims 28 to 77, characterized in that the casing comprises an insulating material impermeable to body fluids.

79. Oral drug dosage form according to claim 78, characterized in that the insulating material comprises one or more of ethylcellulose (EC), dibutyl sebacate (DBS), and titanium dioxide.

80. Oral drug dosage form, according to claim 78 or 79, characterized in that the insulating material is a non-erodible material.

81. Oral drug dosage form, according to any one of claims 78 to 80, characterized in that the insulating material is an erodible material with a pH-based erosion Petition 870250088298, dated 09 / 29 / 2025, p. 213 / 266 16 / 28 and / or an erosion rate that allows complete release of the drug from the oral drug dosage form before the drug component is exposed to body fluids due to erosion of the shell.

82. Oral drug dosage form, according to any one of claims 1 to 81, characterized in that it further comprises a second pH-based enteric element.

83. Oral drug dosage form according to claim 82, characterized in that the pH-based enteric element erodes from the oral drug dosage form at or above a pH value of about 5.5 or a part thereof.

84. Oral drug dosage form according to claim 82 or 83, characterized in that the second pH-based enteric element erodes from the oral drug dosage form at or above a pH value of about 6.8 or a part thereof.

85. A commercial batch of an oral drug dosage form, as defined in any one of claims 1 to 84, characterized in that the commercial batch has a standard deviation of about 0.05 or less for each of the following: an amount of a drug in the oral drug dosage form; a weight of the oral drug dosage form; a maximum transverse dimension of the oral drug dosage form; and a transverse dimension perpendicular to the maximum transverse dimension of the oral drug dosage form.

86. Commercial batch, according to claim 85, characterized in that the commercial batch comprises at least about 1000 of the oral drug dosage forms. Petition 870250088298, dated 09 / 29 / 2025, pp. 214 / 266 17 / 28 87. A three-dimensional (3D) printing method of an oral drug dosage form, as defined in any one of claims 1 to 84, characterized in that it comprises dispensing materials according to a layer-by-layer model of the oral drug dosage form to print the oral drug dosage form, wherein each layer of the layer-by-layer model is printed by dispensing, as required, a layer of: (a) a shell material to form any part of a shell in the layer; (b) a drug component material to form any part of a drug component in the layer; (c) a pH-based enteric element material to form any part of a pH-based enteric element in the layer; (d) an erodible retardant element material to form any part of an erodible retardant element in the layer;(e) a bacterial degradation element material to form any part of a bacterial degradation element in the layer; and (f) an excipient component material to form any part of an excipient component in the layer.

88. Method according to claim 87, characterized in that it further comprises generating the layer-by-layer model of the oral drug dosage form.

89. Method according to claim 87 or 88, characterized in that the dispensing is done by extrusion-melt deposition (MED).

90. Method, according to any one of claims 87 to 89, characterized in that the dispensing of the packaging material, the dispensing of the drug component material, the dispensing of the pH-based enteric element material, the dispensing of the erodible retardant element material, and the dispensing of the packaging material are each performed by a different print head.

91. A method for treating a condition in an individual, characterized in that it comprises administering to the individual an oral drug dosage form as defined in any one of claims 1 to 84.

92. Method, according to claim 91, characterized in that the condition is selected from the group consisting of gastrointestinal disorder, central nervous system (CNS) disorder, cardiovascular disease, hypertension, atherosclerosis, angina, arterial obstruction, peripheral arterial disease, myocardial pathology, arrhythmia, acute myocardial infarction, angina, cardiomyopathy, congestive heart failure, coronary artery disease (CAD), carotid artery disease, endocarditis, hypercholesterolemia, hyperlipidemia, peripheral arterial disease (PAD), genitourinary disorders;Erectile dysfunction, urinary tract diseases, benign prostatic hypertrophy (BPH), renal tubular acidosis, diabetic nephropathy, glomerulonephritis, glomerulosclerosis, urinary tract infection, fecal incontinence, eye diseases, glaucoma, blepharitis, ocular hypertension, retinopathy, conjunctivitis, scleritis, retinitis, keratitis, corneal ulcer, iritis, chorioretinal inflammation, macular edema, xerophthalmia; Pulmonary diseases, asthma, pulmonary hypertension, acute respiratory distress syndrome, COPD, emphysema, pneumonia, tuberculosis, bronchitis, acute bronchitis, bronchiectasis, bronchiolitis, bronchopulmonary dysplasia, byssinosis, coccidioidomycosis (Cocci), cystic fibrosis, influenza, lung cancer, mesothelioma, metabolic diseases, hypercalciuria, hyperglycemia, hyperinsulinemic hypoglycemia, hyperinsulinism, hyperlysinuria and hypoglycemia. Petition 870250088298, dated 09 / 29 / 2025, pp. 216 / 266 19 / 28; 93. Method according to claim 92, characterized in that the gastrointestinal disorder is selected from the group consisting of irritable bowel disease (IBD), irritable bowel syndrome (IBS), constipation, diarrhea, infection and carcinoma.

94. Method according to claim 93, characterized in that IBD is associated with Crohn's disease or ulcerative colitis.

95. Method according to claim 93, characterized in that the carcinoma is colon cancer or colorectal cancer.

96. Method according to claim 93, characterized in that the CNS disorder is selected from the group consisting of neurogenic pain, stroke, dementia, Alzheimer's disease, Parkinson's disease, neuronal degeneration, meningitis, spinal cord injury, cerebral vasospasm and amyotrophic lateral sclerosis.

97. A method for providing local release of a drug in the colon of an individual, characterized in that it comprises administering to the individual an oral drug dosage form as defined in any one of claims 1 to 84, wherein the individual is suffering from a gastrointestinal disorder.

98. Method for providing systemic delivery of a drug to an individual, characterized in that it comprises administering to the individual an oral drug dosage form as defined in any of claims 1 to 84, wherein the individual is suffering from central nervous system (CNS) disorder, cardiovascular disease, hypertension, atherosclerosis, angina, arterial obstruction, peripheral arterial disease, myocardial pathology, arrhythmia, acute myocardial infarction, angina, cardiomyopathy, congestive heart failure, coronary artery disease (CAD), carotid artery disease, endocarditis, hypercholesterolemia, hyperlipidemia, peripheral arterial disease. Petition 870250088298, dated 09 / 29 / 2025, p.217 / 266 20 / 28 (DAP), genitourinary disorders; Erectile dysfunction, urinary tract diseases, benign prostatic hypertrophy (BPH), renal tubular acidosis, diabetic nephropathy, glomerulonephritis, glomerulosclerosis, urinary tract infection, fecal incontinence, eye disease, glaucoma, blepharitis, ocular hypertension, retinopathy, conjunctivitis, scleritis, retinitis, keratitis, corneal ulcer, iritis, chorioretinal inflammation, macular edema, xerophthalmia, lung disease, asthma, pulmonary hypertension, acute respiratory distress syndrome, COPD, emphysema, pneumonia, tuberculosis, bronchitis, acute bronchitis, bronchiectasis, bronchiolitis, bronchopulmonary dysplasia, byssinosis, coccidioidomycosis (Cocci), cystic fibrosis, influenza, lung cancer, mesothelioma, metabolic disease, hypercalciuria, hyperglycemia, hyperinsulinemic hypoglycemia, hyperinsulinism, hyperlysinuria or hypoglycemia.

99. A method for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, characterized in that the oral drug dosage form comprises: a drug component comprising: a first erodible material mixed with a drug, and a first erodible tracking strip; and an envelope comprising a second tracking strip; a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value, wherein the pH-based enteric element comprises a third erodible tracking strip;and Petition 870250088298, dated 09 / 29 / 2025, page 218 / 266 21 / 28 an erodible retardant element comprising a second erodible material, wherein the erodible retardant element comprises a fourth erodible tracking strip, wherein the pH-based enteric element, alone or in combination with the casing, prevents erosion of the erodible retardant element, and wherein the erodible retardant element, alone or in combination with the casing, prevents erosion of the drug component, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over time to obtain the location of the oral drug dosage form and a state of the first erodible tracking strip, the second erodible tracking strip, the third erodible tracking strip and the fourth tracking strip;and (c) adjust the drug component and / or the delay component and / or the shell, or part thereof, based on the location and state of the first erodible tracking band, the second erodible tracking band, the third erodible tracking band, and the fourth tracking band to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

100. Method according to claim 99, characterized in that the adjustment of the delay component comprises adjusting the pH-based enteric element by altering one or more of the following: composition, surface area exposed to body fluid after administration, or thickness of the pH-based enteric element. Petition 870250088298, dated 09 / 29 / 2025, pp. 219 / 266 22 / 28 101. Method according to claim 99 or 100, characterized in that the adjustment of the retardant component comprises adjusting the erodible retardant element by altering one or more of the following: composition, surface area exposed to body fluid after administration, or thickness of the erodible retardant element.

102. A method for treating ulcerative colitis, characterized in that it comprises administering to a human individual an oral drug dosage form as defined in any one of claims 1 to 84, wherein the oral drug dosage form comprises a JAK inhibitor.

103. Method according to claim 102, characterized in that the JAK inhibitor comprises tofacitinib.

104. Method according to claim 103, characterized in that the oral drug dosage form comprises about 11 mg or less of tofacitinib.

105. Method according to claim 103 or 104, characterized in that the oral drug dosage form comprises about 5.5 mg or less of tofacitinib.

106. Method, according to any one of claims 99 to 105, characterized in that the oral drug dosage form is administered once daily.

107. Method for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, characterized in that the oral drug dosage form comprises: a drug component comprising: a first erodible material mixed with a drug, and a first erodible tracking strip; and an envelope; Petition 870250088298, dated 29 / 09 / 2025, p. 220 / 266 23 / 28 a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value;and an erodible retardant element comprising a second erodible material, wherein the pH-based enteric element, alone or in combination with the shell, prevents erosion of the erodible retardant element, and wherein the erodible retardant element, alone or in combination with the shell, prevents erosion of the drug component, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over a period of time to determine the location of the oral drug dosage form and the state of the first erodible tracking band; and (c) adjusting the drug component and / or the retardant component and / or the shell, or part thereof, based on the location and state of the first erodible tracking band, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

108. Method according to claim 107, characterized in that the first erodible material mixed with the drug and the first erodible tracking strip are not in direct contact with each other.

109. Method according to claim 107 or 108, characterized in that the enclosure comprises a second tracking strip, and wherein the second tracking strip is configured to be imaged in order to obtain a state of the second tracking strip.

110. Method according to claim 109, characterized in that the adjustment is based on the location and state of the first erodible tracking strip and / or the second tracking strip.

111. A method according to any one of claims 107 to 110, characterized in that the pH-based enteric element comprises a third tracking band, and in that the third tracking band is configured to be imaged in such a way as to obtain the erodible state of the third tracking band.

112. Method according to claim 111, characterized in that the adjustment is based on the location and state of the first erodible tracking strip and / or the second tracking strip and / or the third erodible tracking strip.

113. Method, according to any one of claims 107 to 112, characterized in that the erodible retardation element comprises a fourth tracking strip, and in that the fourth tracking strip is configured to be imaged in order to obtain a state of the erodible fourth tracking strip.

114. Method according to claim 113, characterized in that the adjustment is based on the location and state of the first erodible tracking strip and / or the second tracking strip and / or the third erodible tracking strip and / or the fourth erodible tracking strip.

115. Method, according to any one of claims 107 to 114, characterized in that obtaining images Petition 870250088298, dated 09 / 29 / 2025, pp. 222 / 266 25 / 28 provides a location of the oral drug dosage form when the first erodible tracking band begins to erode.

116. A method according to any one of claims 107 to 115, characterized in that obtaining images provides a location of the oral drug dosage form when the first erodible tracking band has completely eroded.

117. A method according to any one of claims 107 to 116, characterized in that the adjustment comprises adjusting the delay component, or a portion thereof, to increase the delay in drug release from the oral drug dosage form based on the location and state of the first erodible tracking band indicating earlier release relative to that desired.

118. Method, according to any one of claims 107 to 113, characterized in that the adjustment comprises adjusting the delay component, or part thereof, to decrease the delay in drug release from the oral drug dosage form based on the location and state of the first erodible tracking band indicating a later release relative to that desired.

119. Method for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, characterized in that the oral drug dosage form comprises: a drug component comprising a first erodible material mixed with a drug; a shell; and a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value; and Petition 870250088298, dated 09 / 29 / 2025, p.223 / 266 26 / 28 an erodible delay element comprising a second erodible material, wherein the pH-based enteric element prevents erosion of the erodible delay element, and wherein the erodible delay element prevents erosion of the drug component, wherein the oral drug dosage form comprises at least one tracking strip positioned on a component thereof, the method comprising: (a) administering the oral drug dosage form to an individual; (b) obtaining images of the individual over a period of time to obtain a location of the oral drug dosage form and a state of at least one tracking strip; and (c) adjusting the drug component and / or delay component and / or shell, or portion thereof, based on the location and state of at least one tracking strip, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

120. Method according to claim 119, characterized in that a tracking strip is located on, or near, the drug component.

121. Method according to claim 119 or 120, characterized in that a tracking strip is located on the casing.

122. Method, according to any one of claims 119 to 121, characterized in that a tracking strip is located on the pH-based enteric element. Petition 870250088298, dated 09 / 29 / 2025, pp. 224 / 266 27 / 28 123. Method, according to any one of claims 119 to 122, characterized in that a tracking strip is located on the erodible retarding element.

124. A method according to any one of claims 119 to 123, characterized in that at least one of the at least one tracking strip is erodible.

125. A method for designing an oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual, characterized in that the oral drug dosage form comprises: a drug component comprising a first erodible material mixed with a drug; and a delay component not mixed with the drug, the delay component comprising: a pH-based enteric element configured to erode at or above a predetermined pH value; and an erodible delay element comprising a second erodible material, wherein the pH-based enteric element prevents erosion of the erodible delay element, and wherein the erodible delay element prevents erosion of the drug component, wherein the oral drug dosage form comprises at least one tracking strip positioned on a component thereof, the method comprising: (a) administering the oral drug dosage form to an individual;Petition 870250088298, dated 09 / 29 / 2025, pp. 225 / 266 28 / 28 (b) obtain images of the individual over a period of time to obtain a site of the oral drug dosage form and a state of at least one tracking strip; and (c) adjust the drug component and / or the delay component, or portion thereof, based on the site and state of at least one tracking strip, to design the oral drug dosage form configured to release a drug at a desired gastrointestinal site in an individual.

126. Method according to claim 125, characterized in that a tracking strip is located on, or near, the drug component.

127. Method according to claim 125 or 126, characterized in that a tracking strip is located on the pH-based enteric element.

128. Method, according to any one of claims 125 to 127, characterized in that a tracking strip is located on the erodible retarding element.

129. Method, according to any one of claims 125 to 128, characterized in that at least one of the tracking strips is erodible.

Images