Self-administrable stable injectable pharmaceutical composition
The self-administrable delivery device with cerium glass cartridges and gamma-sterilized teduglutide formulation addresses stability and handling issues, providing a stable and efficient teduglutide delivery system.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- ORBICULAR PHARMA TECH PVT LTD
- Filing Date
- 2026-01-19
- Publication Date
- 2026-07-23
AI Technical Summary
Existing teduglutide formulations require reconstitution before use, leading to issues with dose accuracy, handling efficiency, and environmental waste, and lack a stable delivery system for prolonged storage.
A self-administrable delivery device with a cartridge made of cerium glass, terminally sterilized by gamma irradiation, containing lyophilized teduglutide in one chamber and a solvent in another, which reconstitutes rapidly at administration.
Ensures stable and efficient delivery of teduglutide with improved handling and reduced waste, maintaining long-term stability and ease of use.
Smart Images
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Abstract
Description
[0001] “SELF-ADMINISTRABLE STABLE INJECTABLE PHARMACEUTICAL COMPOSITION”
[0002] FIELD OF THE INVENTION:
[0003] The present invention relates to a self-administrable stable injectable pharmaceutical composition. The present invention relates to a novel delivery device for teduglutide or pharmaceutically acceptable salt or derivative(s) thereof. The present invention relates to a novel delivery device used for delivering one or more dose(s) of teduglutide or salt thereof. Further the present invention relates to a novel delivery device comprising pharmaceutical composition of teduglutide or salt thereof in one chamber and solvent in another chamber of cartridge. The present invention also relates to a novel delivery device comprises cartridge made up with cerium glass which is terminal sterilized and wherein such composition exhibits long-term stability suitable for storage.
[0004] BACKGROUND OF THE INVENTION:
[0005] Currently Teduglutide (GATTEX) is commercially available as a white, lyophilized powder for reconstitution in a sterile, single-dose glass vial with 0.5 m Sterile Water for Injection in a single-dose prefilled syringe. The product to be dispensed is either a one-vial kit or a 30-vial kit.
[0006]
[0007] Teduglutide Structural Formula
[0008] United states 5789379 patent discloses Glucagon-like peptide-2 analogs. Further their formulation as pharmaceutical, and therapeutic use in treating disorders of the small bowel, are described.
[0009] United states 7847061 patent discloses treatment of short bowel syndrome patients with colon-in-continuity. Further discloses glucagon-like peptide 2 (GLP-2) and other GLP-2 receptoragonists effective to improve intestinal function particularly in patients presenting with short bowel syndrome with colon-in-continuity.
[0010] United states 7056886 patent discloses GLP-2 formulations. Further discloses the h[Gly2]GLP-2 lyophilized formulation comprising in the reconstituted product: phosphate buffer in an amount necessary to maintain the pH of the reconstituted product pH of about 7.3 to about 7.4; about 0.5 to about 1% L-histidine; about 3% mannitol.
[0011] United states 8114959 patent is related to a method for increasing the shelf-life of a pharmaceutical composition that comprises a glucagon-like peptide. The method comprises drying, preferably freeze drying, the peptide product at a pH above neutral pH.
[0012] United states 9580487 patent is related to a method of treating stomach or bowel-related disorders by administering glucagon-like-peptide-2 (GUP-2) analogues. The composition contains ZP 1846, histidine, arginine, mannitol, trehalose and acetic acid or m histidine to adjust the pH.
[0013] United states 20240082479 patent publication discloses fluid delivery system container and method of use. Further discloses the administration of fluid therapeutics often involves mixing substances to form (e.g., reconstitute) the fluid therapeutic (e.g., drug in liquid form) and the subsequent delivery of the liquid drug to the patient.
[0014] United states 20240082493 patent publication discloses fluid delivery devices and methods thereof. Further disclosure relates to drug reconstitution devices having a plurality of components movable with respect to one another such that an active agent and a solvent can be reconstituted within the device prior to injection.
[0015] PCT Application WO2018142363 discloses ready to use compositions of glp-2 analogues through self-administrable devices. Further discloses stable ready-to-use pharmaceutical preparation of GUP-2 analogue for parenteral administration, wherein the preparation comprises GUP-2 analogue or its pharmaceutically acceptable salt thereof, U-histidine and pharmaceutically acceptable excipients and the preparation are administered as multi-dose fixed dose and / or single dose injections through self-administrable devices.The important technical challenge to ensure prolonged stability during storage (shelf life) of many peptide-based drug products due to the inherent lability of macromolecules. Hence, proteins are sensitive to both chemical and physical degradation unlike many small molecules. Chemical degradation involves covalent bonds, such as hydrolysis, racemization, oxidation or crosslinking. Physical degradation involves conformational changes relative to the native structure, which includes loss of higher order structure, aggregation, precipitation or adsorption to surfaces. GLP-2 is known to be prone to instability due to aggregation. The liquid formulation of peptide is more preferable but limited because of stability of peptides in liquid during shelflife. Therefore, to achieve the acceptable shelflife of peptide formulation there are various formulation approaches adopted such as stabilization by structural modification, lyophilization, use of protein stabilizers, pH adjustment, storage under specific conditions, stabilization by variety of excipient(s), stabilizing buffers, salts, bases, counterions, metal ions, amino acids and the like.
[0016] The major drawbacks of the approved GATTEX (teduglutide) for injection is supplied as 5 mg of teduglutide as a white, lyophilized powder for reconstitution in a sterile, single-dose glass vial with 0.5 m sterile water for injection in a single-dose prefilled syringe; reconstitution and administration by subcutaneous injection. In addition to the active pharmaceutical ingredient (teduglutide), each vial of GATTEX contains 3.434 mg dibasic sodium phosphate heptahydrate, 3.88 mg L-histidine, 15 mg mannitol, and 0.644 mg monobasic sodium phosphate monohydrate as excipients. No preservatives are present. The product to be dispensed is either a one-vial kit or a 30-vial kit. So, before use a patient needs to reconstitute the lyophilized powder then he / she can administer. For the complete time period of the therapy, patients need to take these approved products. When lyophilized compounds are reconstituted separately it can impact both dose accuracy and handling efficiency. This is not patient friendly for easy to handle, not a cost-effective therapy for patient, and it also effect on environment also by generating waste.
[0017] Thus, there is an unmet need to provide a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition. More generally, there remains a need for delivery devices with stable teduglutide formulation and methods that enable enhanced drug delivery, when delivery device is administered parenterally to patients. Inventors of the present invention have surprisingly found that a teduglutide stableformulation with self-administrable novel delivery device wherein device cartridge comprises cerium glass which is terminal sterilization by gamma irradiation.
[0018] OBJECT OF THE INVENTION:
[0019] It is object of the present invention relates to a self-administrable novel delivery device.
[0020] It is another object of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition
[0021] It is another object of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, wherein device comprises cartridge which is terminal sterilized.
[0022] It is another object of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, wherein device comprises cartridge made up with cerium glass which is terminal sterilized by gamma irradiation.
[0023] It is another object of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition wherein lyophilized teduglutide or pharmaceutically acceptable salts thereof in one chamber and a solvent in another chamber of cartridge, wherein the content of the first chamber gets reconstituted rapidly with the solvent of another chamber at the time of administration.
[0024] It is another object of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, wherein composition is used for the treatment of teduglutide sensitive diseases or disorders.
[0025] SUMMARY OF THE INVENTION:
[0026] The present invention relates to a self-administrable novel delivery device.
[0027] The present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical compositionThe present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, wherein lyophilized teduglutide or salt or derivative thereof in one chamber and a solvent in another chamber of cartridge.
[0028] The present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, wherein lyophilized teduglutide or salt or derivative thereof in one chamber of cartridge in an amount about 2 mg to about 5 mg.
[0029] The present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition wherein lyophilized teduglutide or salt or derivative thereof in one chamber and a solvent in another chamber of cartridge, wherein device cartridge comprises cerium glass which is terminal sterilization by gamma irradiation.
[0030] The present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition wherein lyophilized teduglutide or salt or derivative thereof in one chamber and a solvent in another chamber of cartridge, wherein the content of the first chamber of cartridge gets reconstituted rapidly with the solvent of another chamber of cartridge at the time of administration.
[0031] The present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, wherein composition is used for the treatment of teduglutide sensitive diseases or disorders.
[0032] DETAILED DESCRIPTION:
[0033] The present invention relates to a self-administrable stable injectable pharmaceutical composition. The present invention relates to a novel delivery device for teduglutide or pharmaceutically acceptable salt or derivative(s) thereof. The present invention relates to a novel delivery device used for delivering one or more dose(s) of teduglutide or salt or derivative thereof. Further the present invention relates to a novel delivery device comprisingpharmaceutical composition of teduglutide or salt or derivative thereof in one chamber and solvent in another chamber of cartridge. The present invention also relates to a novel delivery device comprises cartridge made up with cerium glass which is terminal sterilized and wherein such composition exhibits long-term stability suitable for storage.
[0034] The present invention relates to a stable injectable composition, comprising active pharmaceutical ingredient is teduglutide or salt or derivative thereof, with one or more pharmaceutically acceptable excipient(s).
[0035] As used herein, the words or terms set forth below have the following definitions:
[0036] “Delivery device” or “Novel delivery device” refers to injection pen. Each delivery device may comprise one of the cartridge assemblies and one of the dose setting members connected to each other to form the delivery device. Each delivery device is preferably an injection device such as, for example, an injection pen, single dose pen or multi dose pen, autoinjector, prefilled syringe, pre-filled syringe fully assembled into an auto-injector device, pre-filled syringe fully assembled into an multi dose device and the like.
[0037] The term "active pharmaceutical ingredient" or "drug" or “API” refers to a substance that has a physiological effect when ingested or otherwise introduced into the body, in particular or a chemical substance used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well- being. The "active pharmaceutical ingredient" or "drug" or “API” is GLP-2 peptide or its analogue or its derivative or its metabolite or optical isomer, diastereomer, enantiomer, tautomer, or physiologically acceptable salt and solvates thereof.
[0038] The term “GLP-2 peptide” as used herein means GLP-2(l-33), a GLP-2 analogue, a GLP-2 derivative or a derivative of a GLP-2 analogue or any pharmaceutically acceptable salt thereof. Preferably GLP-2 peptide is teduglutide or h[Gly2]GLP-2.
[0039] The term “pharmaceutically acceptable” means approved by a regulatory agency or listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia or formulary and the like for use in mammals, and more particularly in humans.The term "pharmaceutically acceptable salts" or “salts thereof’ refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts, solvate, hydrate, esters and the like thereof. Pharmaceutically acceptable salt forms of compounds provided herein are synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods.
[0040] The term “amount” as used herein refers to quantity or to concentration as appropriate to the context.
[0041] The term "composition" or "formulation" or "preparation" is intended to encompass a combination including active ingredients and pharmaceutically acceptable excipients, as well as any product which results, directly or indirectly, from combination, complexation, or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions involving one or more of the ingredients. The term "formulation" or "dosage form" or "composition" refers to finished pharmaceutical products that are suitable for administration, including, but not limited to, injections, etc.
[0042] The “pharmaceutical composition” described herein include one or more active pharmaceutical ingredients. Any suitable active pharmaceutical ingredient can be employed, in any suitable amount, provided it effectively treats the disease or disorder in the subject. The amount of active pharmaceutical ingredient employed will typically depend on the active pharmaceutical ingredient as well as the disease or disorder to be treated.
[0043] The “stable pharmaceutical composition” described herein include one or more active pharmaceutical ingredient(s) with pharmaceutical acceptable excipient(s) having physical and chemical stability.
[0044] The “stable GLP-2 peptide pharmaceutical composition” described herein include one or more GLP-2 peptide comprises of sodium with pharmaceutical acceptable excipient(s) having physical and chemical stability.The “stable teduglutide injectable pharmaceutical composition” described herein include lyophilized powder comprises teduglutide or salt or derivative thereof with pharmaceutical acceptable excipient(s) having physical and chemical stability.
[0045] As used herein, the term “lyophilized powder” or “lyophilized preparation” refers to any solid material obtained by lyophilization, i.e., freeze-drying of an aqueous solution. As used herein, the term “lyophilized teduglutide or salt or derivative thereof’ refers to lyophilization of teduglutide or salt or derivative thereof with one or more pharmaceutically acceptable excipient(s).
[0046] The term "parenteral” as used herein the compositions are administered by injection, infusion, or implantation into the human body. They may be directly administered or diluted before administration. The term "parenteral administration" as used herein is intramuscular, intraperitoneal, intra-abdominal, subcutaneous, intravenous, intraarterial, intradermal, intravitreal, intracerebral, intrathecal, epidural administration. In some embodiments, administration is subcutaneous.
[0047] The term "carrier" or "vehicle" or "solvent" or “diluent” or “excipient” or “excipient(s)” as used herein refers to pharmacologically inert materials that provide a more or less fluid matrix, suitable for parenteral drug administration. Carriers, vehicles or diluent useful herein include any such materials known in the art, which are nontoxic and do not interact with other components of a pharmaceutical formulation or drug delivery system in a deleterious manner.
[0048] The term “about” or “approximately” means within 10% of a given value or range or within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. Alternatively, the term “about” means within an acceptable standard error of the mean.
[0049] The term "stability" or "stable" as used herein includes both physical and chemical stability. Stability parameters include but not limited to potency, stable pH value and other physicochemical parameters. Peptide formulations are widely used as medicine. The most of the peptide drugs are formulated as liquid injectable compositions. The pharmaceutical compositions of such peptides are required to be stable or to have shelflife of several years inorder to be suitable for use as medicine. However, peptide compositions are inherently unstable due to sensitivity towards physical and chemical degradation. Physical degradation involves transformations in the secondary, tertiary, or quaternary structure of the molecule or any conformational changes in the native structure of peptides, which may lead to aggregation, formation of fibrils, precipitation or surface adsorption. Chemical degradation change of covalent bonds, such as oxidation, hydrolysis, racemization or crosslinking. To ensure the products safety and efficacy, peptide formulation must meet defined quality and stability during and / or immediately after manufacture as well at the end of their designated shelf lives or during storage.
[0050] The term “terminal sterilization” as used herein refers to a process whereby a product is sterilized in its final container or packaging, which permits the measurement and evaluation of quantifiable microbial lethality. Terminal sterilization refers to a sterility assurance level (SAL) of 10 and describes the process that ensures that the devices are sterile at the point of use. Microorganisms are directly killed by ionizing radiation, or by the heat generated by microwave radiation. In Radiation method, ionizing radiations which may be used are gamma rays emitted from a radioisotope such as cobalt 60, an electron beam and bremsstrahlung (X rays) generated from an electron accelerator.
[0051] One embodiment of the present invention relates to a novel delivery device.
[0052] Another embodiment of the present invention related to a novel delivery device is terminal sterilized.
[0053] Another embodiment of the present invention related to a novel delivery device is terminal sterilized with gamma irradiation.
[0054] Another embodiment of the present invention related to a novel delivery device which comprises cartridge made up with the cerium glass.
[0055] Another embodiment of the present invention relates to novel delivery device which comprises cartridge made up with the cerium glass has terminally sterilized.Another embodiment of the present invention relates to novel delivery device which comprises cartridge made up with the cerium glass has terminally sterilized by gamma irradiation.
[0056] Another embodiment of the present invention relates to novel delivery device which comprises cartridge made up with the cerium glass to provide irradiation stability with respect to coloration.
[0057] Another embodiment of the present invention relates to a novel delivery device is a self-administrable.
[0058] Another embodiment of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition.
[0059] Another embodiment of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, comprises cartridge has two chambers.
[0060] Another embodiment of the present invention relates to a novel delivery device comprises two individual chambers.
[0061] Another embodiment of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, comprises cartridge selected from the glass, plastic and the like.
[0062] Another embodiment of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, comprises glass cartridge.
[0063] Another embodiment of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, comprises glass cartridge with cerium.Another embodiment of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition, comprises glass cartridge with cerium wherein lyophilized teduglutide or salt or derivative thereof in one chamber and a solvent in another chamber of cartridge.
[0064] Another embodiment of the present invention relates to a self-administrable novel delivery device which is terminal sterilization.
[0065] Another embodiment of the present invention relates to a self-administrable novel delivery device which is terminal sterilization by radiation.
[0066] Another embodiment of the present invention relates to a self-administrable novel delivery device capable of delivering stable teduglutide injectable pharmaceutical composition which is terminal sterilization by radiation.
[0067] Another embodiment of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition wherein lyophilized teduglutide or salt or derivative thereof in one chamber and a solvent in another chamber of cartridge, wherein final product is terminally sterilized to avoid sterility issue.
[0068] Another embodiment of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition wherein lyophilized teduglutide or salt or derivative thereof in one chamber and a solvent in another chamber of cartridge, wherein device cartridge comprises cerium glass which is terminal sterilization by gamma irradiation.
[0069] Another embodiment of the present invention relates to a self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition wherein lyophilized teduglutide or salt or derivative thereof in one chamber and a solvent in another chamber of cartridge, wherein the content of the first chamber of cartridge gets reconstituted rapidly with the solvent of another chamber of cartridge at the time of administration.In one embodiment of present invention comprises GLP-2 peptide is teduglutide or (Gly2)GLP-2 or h[Gly2] GLP-2.
[0070] Teduglutide is a single-chain polypeptide with 33 amino acids having a mass of 3750.5 Da. It has no disulfide bonds, no glycosylation sites, and no post-translational modifications. Structural investigations of teduglutide show that the peptide contains varying amounts of a-helix and P-sheet secondary structures, depending on the peptide concentration and surrounding conditions.
[0071] In one embodiment of present invention provides a self-administrable novel delivery device of stable teduglutide composition.
[0072] In another embodiment of present invention provides a novel delivery device comprises reservoir or cartridge. In another embodiment of present invention provides a novel delivery device comprises reservoir or cartridge having 0.3 ml to 10 ml capacity.
[0073] In another embodiment of present invention provides a self-administrable injectable device comprising pharmaceutical composition.
[0074] In one embodiment of present invention provides a self-administrable injectable device comprising the pharmaceutical composition of:
[0075] a) Active pharmaceutical ingredient;
[0076] b) one or more pharmaceutically acceptable excipient(s).
[0077] In another embodiment of present invention provides a self-administrable injectable device comprising pharmaceutical composition of:
[0078] a) Active pharmaceutical ingredient as teduglutide or salt or derivative thereof;
[0079] b) optionally preservative; and
[0080] c) one or more pharmaceutically acceptable excipient(s).
[0081] In another embodiment of present invention provides a self-administrable injectable device comprising pharmaceutical composition of:
[0082] a) teduglutide or salt or derivative thereof;b) dibasic sodium phosphate heptahydrate;
[0083] c) L-histidine;
[0084] d) mannitol;
[0085] e) monobasic sodium phosphate monohydrate;
[0086] f) sterile water for injection; and
[0087] g) one or more pharmaceutically acceptable excipient(s).
[0088] In another embodiment of present invention provides a self-administrable injectable device comprising pharmaceutical composition of:
[0089] a) teduglutide or salt or derivative thereof about 5 mg / mL to about 50 mg / mL;
[0090] b) dibasic sodium phosphate heptahydrate about 2 mg / mL to about 15 mg / mL;
[0091] c) L-histidine about 1 mg / mL to about 25 mg / mL;
[0092] d) mannitol about 10 mg / mL to about 120 mg / mL;
[0093] e) monobasic sodium phosphate monohydrate about 0.2 mg / mL to about 5 mg / mL; f) sterile water for injection; and
[0094] g) one or more pharmaceutically acceptable excipient(s).
[0095] In another embodiment of present invention provides a self-administrable injectable device comprising pharmaceutical composition; wherein composition is having pH in a range of about 6 to about 8.
[0096] In one embodiment of present invention provides a self-administrable injectable device comprising: a first chamber of cartridge comprising a lyophilized powder and a second chamber of cartridge comprising water for injections to be combined with the lyophilized powder of the first chamber.
[0097] In one embodiment of present invention provides a self-administrable injectable device comprising cartridge in which:
[0098] a first chamber of cartridge comprising a lyophilized powder, where the powder comprises a) teduglutide or salt or derivative thereof;
[0099] b) dibasic sodium phosphate heptahydrate;
[0100] c) L-histidine;
[0101] d) mannitol;
[0102] e) monobasic sodium phosphate monohydrate;f) one or more pharmaceutically acceptable excipient(s); and
[0103] a second chamber of cartridge comprising water for injections to be combined with the lyophilized powder of the first chamber of cartridge ,
[0104] In another embodiment of present invention, the teduglutide or salt or derivative thereof has a concentration of from about 2 mg to 5 mg.
[0105] In another embodiment of present invention, the teduglutide composition has a concentration of from about 5mg / ml to about 50mg / ml.
[0106] In another embodiment, the pharmaceutical composition of present invention further comprises one or more pharmaceutically acceptable excipients such as buffering agent, carrier, pH modifiers, antioxidants, preservatives, chelating agents, bulking agents and lyoprotectants, diluents, solvents and co-solvents, solubilizing, wetting, suspending, emulsifying or thickening agents, bulking agents, bases, counterions and the like or mixtures thereof. The choice of excipients depends on the desired characteristics of the compositions and on the nature of other pharmacologically active compounds in the formulation. Suitable excipients are known to those skilled in the art (see Handbook of Pharmaceutical Excipients, edited by Rowe et al, 6thedition, 2009).
[0107] In one embodiment, the present invention provides method or process for preparation:
[0108] 1. Dispensed quantity of purified water was transferred into a clean, dried mixing vessel. 2. Dispensed quantity of excipients was added in to step 1, under constant stirring with appropriate time and speed.
[0109] 3. Dispensed quantity of teduglutide or salt or derivative thereof was added in to step 2, under constant stirring with appropriate time and speed.
[0110] 4. Step 3, filled in first chamber of novel delivery device and solvent filled in second chamber of novel delivery device, and first chamber of device was subjected to lyophilization. 5. Device was terminal sterilized by gamma irradiation.
[0111] In another embodiment, the present invention provides method or process for preparation: 1. Dispensed quantity of purified water was transferred into a clean, dried mixing vessel. 2. Dispensed quantity of excipients was added in to step 1, under constant stirring with appropriate time and speed.3. Dispensed quantity of teduglutide or salt or derivative thereof was added in to step 2, under constant stirring with appropriate time and speed.
[0112] 4. Step 3, solution subjected to lyophilization.
[0113] 5. Step 4, fdled in first chamber of novel delivery device and solvent filled in second chamber of novel delivery device.
[0114] 6. Device was terminal sterilized by gamma irradiation.
[0115] In another embodiment, the present invention provides method or process for preparation: 1. Lyophilised premix of teduglutide or salt or derivative thereof and excipients was filled in novel delivery device.
[0116] 2. Device was terminal sterilized by gamma irradiation.
[0117] In another embodiment, the present invention provides method or process for preparation: 1. Premix of teduglutide or salt or derivative thereof and excipients was filled in novel delivery device.
[0118] 2. Step 1 was subjected to lyophilization.
[0119] 3. Device was terminal sterilized by gamma irradiation.
[0120] In another embodiment, the present invention provides method or process for preparation: 1. Premix of teduglutide or salt or derivative thereof and excipients.
[0121] 2. Step 1 was subjected to lyophilization.
[0122] 3. Step 2 was filled in first chamber of novel delivery device and solvent in second chamber of novel delivery device.
[0123] 4. Device was terminal sterilized by gamma irradiation.
[0124] In one embodiment of the present invention provides device is terminal sterilized by gamma irradiation before the final packaging of novel delivery device.
[0125] In another embodiment of the present invention provides device terminal sterlization at different time like before filling of lyophilized powder or after filling of lyophilized powder.
[0126] In another embodiment of the present invention provides device terminal sterlization at different time like after the premix of teduglutide or salt or derivative thereof and excipient(s) filled in cartridge of device with subjected to lyophilization.In another embodiment of the present invention provides only cartridge of novel delivery device is terminal sterilized by gamma irradiation.
[0127] In one embodiment of the present invention provides device is terminal sterilized by gamma irradiation wherein in the only teduglutide or salt or derivative thereof lyophilized powder is present in first chamber.
[0128] In one embodiment of the present invention provides device is terminal sterilized by gamma irradiation wherein teduglutide or salt or derivative thereof lyophilized powder is present in first chamber and solvent in another chamber.
[0129] In one embodiment of the present invention provides device comprises the teduglutide solution in one chamber, that solution first lyophilised and then terminal sterilized by gamma irradiation.
[0130] In another embodiment of present invention teduglutide composition can be administered to patients in need of treatment therewith by any appropriate route. Preferably the composition can be administered by different parenteral routes such as but not limited to intradermal, subcutaneous, intramuscular, intravenous, intraperitoneal, intrathecal, epidural, intracardiac, intraarticular, intracavemous, intravitreal and the like.
[0131] In another embodiment of present invention provides stable teduglutide injectable composition can be administered by subcutaneous injection.
[0132] In another embodiment, the present invention compositions comprise a lyophilised powder in one chamber and water in another chamber of cartridge.
[0133] In another embodiment, the present invention injectable composition is prepared by the methods known in the art that maintains sterility, avoid the introduction of contaminants and microbial growth.
[0134] In another embodiment of present invention compositions may be administered by selfadministration injection device is injection pen.In another embodiment of present invention compositions may be administered by selfadministration injection device is a variable device where in device delivered one or more same or different amount of dose.
[0135] In one embodiment, the present invention compositions disclosed herein can be dispensed by suitable device such as single dose pen or multi dose pen and the like.
[0136] In another embodiment of present invention compositions may be administered by selfadministration injection device disclosed herein can be autoinjector, injection pen, prefilled syringe, pre-filled syringe fully assembled into an auto-injector device, pre-filled syringe fully assembled into an multi dose device and the like. In another embodiment of present invention self-administration injection device disclosed herein can be reusable or disposable and the like.
[0137] In another embodiment of present invention injection device disclosed herein can be prefilled dual chamber syringe, dual chamber cartridge and the like.
[0138] In another embodiment of present invention self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition; wherein composition is ready to administer.
[0139] In another embodiment of present invention self-administrable novel delivery device which is capable of delivering stable teduglutide injectable pharmaceutical composition; wherein composition is used for the treatment of teduglutide sensitive diseases or disorders.
[0140] The present invention is further illustrated by reference to the following experiments which is for illustrative purpose only and does not limit the scope of the invention in any way.
[0141] Example:!
[0142] Table 01:
[0143]
[0144]
[0145] * Optionally preservative
[0146] Manufacturing Process:
[0147] Any one method from above-described embodiment was used for manufacturing and sterlization.
[0148] Result:
[0149] Table 02: The assay, aggregate content and RS data is provided in the table below:
[0150]
[0151] From above table it observed that after the gamma sterilization the changes in comparison to control sample are minor and within the acceptable limits. Hence, surprisingly present inventor found that terminal sterilization by gamma irradiation is a suitable method. The novel delivery device comprising teduglutide or salt or derivative thereof, has maintained the physical & chemical stability.
[0152] Although the invention herein has been described with reference to particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention. It is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention as defined by the appended embodiments.
Claims
WE CLAIM1. An injectable pharmaceutical delivery device, comprising: a cartridge having at least two separate chambers, wherein a first chamber contains a pharmaceutical composition comprising teduglutide or a pharmaceutically acceptable salt or derivative thereof, and wherein a second chamber contains a solvent suitable for reconstitution of the pharmaceutical composition, wherein the cartridge is made of cerium glass; wherein the delivery device is self-administrable.
2. The self-administrable delivery device of claim 1, wherein the cartridge is terminally sterilized.
3. The self-administrable delivery device of claim 1 , wherein the pharmaceutical composition exhibits long-term stability suitable for storage prior to administration.
4. The self-administrable delivery device of claim 1, wherein the teduglutide or pharmaceutically acceptable salt thereof is present in a lyophilized form in the first chamber.
5. The self-administrable delivery device of claim 1, wherein the solvent in the second chamber is selected from sterile water for injection, buffered aqueous solutions, or saline solutions.
6. The self-administrable delivery device of claim 1, wherein the device is configured to deliver one or more doses of teduglutide or a pharmaceutically acceptable salt thereof.
7. The self-administrable delivery device of claim 1, wherein mixing of the pharmaceutical composition and the solvent occurs within the cartridge immediately prior to administration.
8. The self-administrable delivery device of claim 1, wherein the delivery device is selected from aprefilled syringe, autoinjector, or pen-type injector.
9. A method of administering teduglutide, comprising: reconstituting a pharmaceutical composition comprising teduglutide or a pharmaceutically acceptable salt or derivative thereof within the delivery device of claim 1, and self-administering the reconstituted composition by injection.
10. An injectable pharmaceutical delivery device comprises pharmaceutical composition according to any one of the preceding claims, wherein the composition is used in the treatment or prevention diseases sensitive to teduglutide.