Local administration of GLP-1 receptor agonists

Abstract

A method for treating type 2 diabetes, chronic weight maintenance, or binge eating involves administering a pharmaceutically effective amount of a topical composition containing a GLP-1 receptor agonist suspended in an anhydrous suspension base into the oral cavity of a subject for oral absorption. The topical composition is prepared to form self-emulsifying liposomes in the aqueous environment of the oral cavity.

Description

[[TECHNICAL FIELD]]

[0001] The present disclosure relates to GLP-1 receptor agonist compositions for topical administration, and methods of production and methods of use thereof. [[BACKGROUND ART]]

[0002] Glucagon-like peptide-1 (GLP-1) receptors are transmembrane receptors that regulate glucose metabolism, insulin production and secretion, glucagon secretion, gastric emptying, and satiety via intracellular signaling pathways. GLP-1 hormone is a ligand for the GLP-1 receptor and is released from L cells in the gastrointestinal tract in response to nutrient intake. Activation of GLP-1 receptors via ligand binding lowers blood glucose levels by promoting insulin secretion and suppressing glucagon secretion. Furthermore, activation delays gastric emptying and interacts with appetite control mechanisms in the brain to transmit satiety signals. GLP-1 receptor agonists mimic the action of GLP-1 hormone and are administered via daily or weekly subcutaneous injection for weight loss and the treatment of type 2 diabetes. Semaglutide, a GLP-1 receptor agonist, is available as a tablet for oral administration and is used for administration to the gastrointestinal tract. [[SUMMARY OF THE INVENTION]]

[0003] In one aspect, a topical composition for oral administration to achieve oral absorption for treating type 2 diabetes, chronic weight management, or hyperphagia comprises a pharmaceutically effective amount of semaglutide suspended in an anhydrous suspension base. The topical composition for oral absorption may further comprise phosphatidylcholine, lysophosphatidylcholine, polycarbophil, glyceryl distearate, glyceryl monostearate, magnesium stearate, microcrystalline cellulose, povidone, and sodium carproate.

[0004] In one example, the topical composition for oral absorption may further comprise caprylic / capric triglyceride.

[0005] In the above or other examples, the topical composition for oral absorption may further include sucralose, monk fruit (Siraitia grosvenori), marshmallow oil fragrance, or a combination thereof.

[0006] In another embodiment, a method for treating type 2 diabetes, chronic weight maintenance, or a state of overeating is provided, which involves administering a pharmaceutically effective amount of semaglutide suspended in an anhydrous suspension base to the oral cavity of a subject for oral absorption. The topical composition further comprises phosphatidylcholine, lysophosphatidylcholine, polycarbophil, glyceryl distearate, and glyceryl monostearate.

[0007] In one example, the topical composition may further include sucralose, monk fruit (Siraitia grosvenori), or both. The topical composition may also include marshmallow oil fragrance.

[0008] In the above or another example, the topical composition further comprises magnesium stearate, microcrystalline cellulose, povidone, and sodium salcaprozate.

[0009] In the above or any other example, the topical composition further comprises caprylic / capric triglyceride.

[0010] In the above or any other example, the topical composition further comprises glyceryl monostearate, glyceryl distearate, or both.

[0011] In yet another embodiment, a method for preparing a topical composition for topical administration into the oral cavity for oral absorption to treat type 2 diabetes, chronic weight maintenance, or a state of overeating comprises mixing semaglutide powder with an anhydrous suspension base to prepare a suspension. The suspension is prepared to form self-emulsifying liposomes in the aqueous environment of the oral cavity.

[0012] In one example, the suspension contains phosphatidylcholine and lysophosphatidylcholine.

[0013] In the above or another example, the suspension further contains polycarbophil.

[0014] In yet another example, the suspension contains glyceryl distearate and glyceryl monostearate.

[0015] In the above or any other example, the suspension further comprises caprylic / capric triglyceride.

[0016] In the above or any other example, the suspension further comprises sucralose, silaitia grosvenori (monk fruit), or both.

[0017] In the above or any other example, the suspension further comprises marshmallow oil flavoring.

[0018] In one example, the suspension further comprises magnesium stearate, microcrystalline cellulose, povidone, sodium salcaprosate, polycarbophil, glyceryl distearate, glyceryl monostearate, phosphatidylcholine, lysophosphatidylcholine, caprylic / capric triglyceride, sucralose, monk fruit (Silla grosvenorii), or a combination thereof.

[0019] In one embodiment, a method for treating type 2 diabetes, chronic weight maintenance, or a state of overeating involves administering a pharmaceutically effective amount of a topical composition comprising semaglutide suspended in an anhydrous suspension base to a subject orally for absorption. The semaglutide may be encapsulated within liposomes suspended in an anhydrous suspension base.

[0020] In one example, the topical composition further includes a fragrance.

[0021] In another aspect, a method for preparing a topical composition for oral absorption via topical administration into the oral cavity comprises mixing semaglutide powder with an anhydrous suspension base to prepare a suspension. The anhydrous suspension base may comprise a liposome system or a mixed micelle system, or the method may further comprise mixing preliposomes to prepare the liposome system or the mixed micelle system. The preliposome system may comprise phospholipids.

[0022] In one example, the mixing further comprises mixing a flavoring agent.

[0023] In yet another aspect, a method for preparing a topical composition for oral absorption via topical administration into the oral cavity comprises mixing semaglutide with a base to prepare a suspension.

[0024] In one example, the suspension is an anhydrous suspension. The flavoring agent may be embedded in the anhydrous suspension base.

[0025] In one example, the mixing further comprises a flavoring agent.

[0026] In one example, semaglutide is mixed with the base in a powdery dosage form. The powdery dosage form may further comprise preliposomes. The powdery dosage form may further comprise a flavoring agent.

[0027] In one example, the base comprises a liposome system or a mixed micelle system.

[0028] In one example, the topical composition is a composition for sublingual administration or buccal administration.

[0029] In yet another aspect, provided is a method for preparing a topical composition for transdermal or transmucosal delivery via topical administration to the skin or the mucosa of the vagina, rectum, oral cavity or nasal cavity of a subject. The method may further comprise mixing semaglutide with a base to prepare a suspension.

[0030] In one example, the suspension is an anhydrous suspension.

[0031] In one example, semaglutide is mixed with a base in a powder dosage form. The powder dosage form may further contain preliposomes.

[0032] In one example, the base includes a liposome system or a mixed micelle system.

[0033] In one example, the base may include a cream, ointment, solution, lotion, suspension, gel, paste, or foam.

[0034] In yet another embodiment, a method for treating type 2 diabetes, chronic weight maintenance, or a state of overeating includes administering a pharmaceutically effective amount of a topical composition comprising a GLP-1 receptor agonist and a base to the skin of a subject or to the mucous membrane of the vagina, rectum, oral cavity, or nasal cavity, by transdermal or transmucosal delivery.

[0035] In one example, the base may include a cream, ointment, solution, lotion, suspension, gel, paste, or foam.

[0036] In one example, the GLP-1 receptor agonist is encapsulated in liposomes or preliposomes suspended in a base, or otherwise associated. The base may be an anhydrous suspension base.

[0037] In one example, a topical composition is prepared to self-emulsify in an aqueous environment and form self-emulsifying liposomes.

[0038] In one example, the topical composition further includes a fragrance.

[0039] In another embodiment, a method for treating type 2 diabetes, chronic weight maintenance, or a state of overeating comprises administering a pharmaceutically effective amount of a topical composition comprising semaglutide suspended in an anhydrous suspension base to a subject for oral absorption.

[0040] In one example, semaglutide is obtained from or derived from crushed commercially available semaglutide-containing oral tablets.

[0041] In one example, the oral tablets consist of RYBELSUS® tablets.

[0042] In yet another embodiment, a method for preparing a topical composition for local administration into the oral cavity for oral absorption includes preparing a suspension by mixing the powder of a pulverized commercially available GLP-1 receptor agonist oral tablet with a base.

[0043] In one example, the GLP-1 receptor agonist is semaglutide. [Modes for carrying out the invention]

[0044] This disclosure describes various embodiments of topical compositions comprising a GLP-1 receptor agonist, as well as methods for manufacturing and using the same. In some embodiments, the GLP-1 receptor agonist may include semaglutide. Additionally or alternatively, the GLP-1 receptor agonist may consist of liraglutide, exenatide, lixisenatide, taspoglutide, rotiglipron, dulaglutide, tylzepatide, albiglutide, danuglipron, orfolglipron, efpeglenatide, or a combination thereof.

[0045] In various embodiments, topical compositions may be prepared for topical administration via mucosal or transdermal routes. For example, topical compositions may be prepared for topical administration to the surface of the skin or mucous membrane. In some examples, topical compositions may be prepared for topical administration to the mucous membrane of a natural opening such as the oral cavity, nasal cavity, vagina, or rectum. In one embodiment, the topical composition comprises an anhydrous suspension prepared to form self-emulsifying liposomes in an aqueous environment.

[0046] As described above, topical compositions may be prepared for topical administration to mucosal tissue, i.e., transmucosal delivery. For example, a topical composition may be administered topically into the oral cavity and absorbed orally within the oral cavity. In yet another example, a topical composition may be administered sublingually, via the buccal mucosa, or by other means into the oral cavity and absorbed orally.

[0047] When GLP-1 receptor agonists are administered orally into the gastrointestinal tract, the plasma albumin binding rate can exceed 99%. Topical administration, such as transmucosal administration via oral absorption, significantly reduces the dosage required to achieve an effect equivalent to or similar to oral administration by neutralizing or minimizing the effects of plasma albumin binding and first-pass metabolism. Therefore, the topical compositions and methods of topical administration described herein may effectively avoid plasma albumin binding and first-pass metabolism. This groundbreaking advance reduces the required dosage and the associated cost to the patient without compromising efficacy. The topical compositions and methods of topical administration described herein may also be used to benefit patients in a similar manner to injectable preparations, but without the hassle, pain, and cost associated with handling injectable preparations.

[0048] In various embodiments, topical compositions may be used to treat type 2 diabetes or weight loss. In some embodiments, topical compositions may also be used to treat behaviors associated with overdose, such as binge eating and / or compulsive behavior. Examples of symptoms include overeating, overdrinking, or shopping-related behaviors, excessive or compulsive use of social media, electronic devices, television, drugs, tobacco, nicotine, shoplifting, or sex addiction. In one example, topical compositions may be used to treat alcohol dependence.

[0049] In various embodiments, the topical composition contains a GLP-1 receptor agonist in a base for topical oral absorption in the oral cavity. The GLP-1 receptor agonist may be selected from semaglutide, liraglutide, exenatide, lixisenatide, taspoglutide, rotiglipron, dulaglutide, tylzepatide, albiglutide, danuglipron, orfolglipron, efpeglenatide, or a combination thereof. Compositions prepared for oral absorption may be in the form of a solution, semi-solid, or solid dosage form. For transmucosal delivery by oral absorption, the topical composition may be in the form of a powder, solution, suspension, gel, paste, tablet, or lozenge dosage form. The topical composition may be in the form of a dry powder, aqueous, colloidal suspension (e.g., emulsion), anhydrous, or other dosage form. For example, the topical composition may be provided as an aqueous or non-aqueous base. The topical composition may be provided in colloidal form such as an emulsion or other suspension. The topical composition may be provided in gel dosage form. Topical compositions may be supplied in solid form.

[0050] Topical compositions may be formulated into various oral absorption forms. For example, in one embodiment, a topical composition may be a solution or suspension for application sublingually or into the buccal mucosa using a syringe or dropper. In one example, a topical composition may include a mouthwash or gargle for transmucosal delivery via the oral cavity. In some embodiments, a topical composition may be prepared for oral absorption containing a fragrance to improve patient compliance by enhancing ease of use and taste. In one embodiment, a topical composition may include a suspension containing a GLP-1 receptor agonist in a base for topical oral absorption. The suspension may be absorbed in the oral cavity, for example, sublingually, through the buccal mucosa, or other routes. In one example, the suspension is an anhydrous suspension. The suspension may contain phospholipids to construct an innovative system for direct delivery of the active ingredient to the sublingual mucosa and / or buccal mucosa. The phospholipids may include lipid aggregates consisting of liposomes, micelles, or both.

[0051] In various embodiments, the topical composition, at the time of administration, comprises semaglutide encapsulated by a liposome system or mixed micelle system, semaglutide associated with a liposome system or mixed micelle system, or semaglutide in the presence of a liposome system or mixed micelle system. The system may be a mixed micelle system containing liposomes or a mixed micelle system without liposomes. The system may contain substantially pure liposomes, and as a result, the system contains aggregated lipids associated mainly or substantially in a bilayer. All or part of the GLP-1 receptor agonist may be encapsulated by liposomes, micelles, or both, or may be associated with liposomes, micelles, or both. In one example, the GLP-1 receptor agonist may not necessarily be encapsulated by liposomes and / or micelles, and may be present in the topical composition in the presence of lipids such as phospholipids, which may include liposomes and / or mixed micelles. GLP-1 receptor agonists may associate with or be present within the liposome bilayer. Topical compositions may take the form of aqueous, colloidal suspensions (e.g., emulsions), anhydrous, or other dosage forms. In one example, the topical composition contains a lipid system, preliposomes, or mixed micelle system in an anhydrous suspension base. The anhydrous suspension base may ensure the stability and efficacy of the liposomes or mixed micelles when activated in an aqueous environment, allowing for optimal performance. In further embodiments, the liposomes or mixed micelle system are contained within the anhydrous suspension base. The anhydrous suspension base may ensure the stability and efficacy of the liposomes, allowing for optimal performance. In some examples, GLP-1 receptor agonists, such as semaglutide, are dissolved in the anhydrous suspension base. Topical compositions may exhibit remarkably high stability. For example, topical compositions may remain stable for 90 days or more. In various embodiments, the topical composition is anhydrous. In further embodiments, liposomes or mixed micelle systems may be used in compositions for transmucosal or transdermal delivery to other body surfaces, such as the skin, nasal cavity, vagina, or rectum. In one embodiment, the topical composition contains polycarbophil to extend the contact time.The topical composition is anhydrous and may be activated by interaction with an aqueous environment, self-emulsifying to form liposomes or mixed micelle systems. In one embodiment for oral absorption, the topical composition uses a film-forming adhesive component that forms a protective film to minimize initial contact between the active ingredient and the taste buds.

[0052] Topical compositions may be provided in any appropriate dose of a GLP-1 receptor agonist, as determined by those skilled in the art based on the information in this disclosure. For various applications, dose selection may take into account one or more of the disease being treated, its severity, the patient's profile, the frequency of administration, the dosage form, or the route of administration. For example, satiety therapy for weight loss may be more appropriate than diabetes therapy. Overeating therapy may be more appropriate than satiety therapy. Heavier patients may be more appropriate than lighter patients. Transdermal administration may be more appropriate than transmucosal administration. Various administration schedules may be used. For example, administration may be once or twice daily, or as prescribed. Depending on the application, administration may be once or twice weekly. Higher doses may be considered appropriate for regimens with lower administration frequencies.

[0053] In various embodiments, the topical composition is administered orally or via other mucosal or dermal routes in an effective dose of 0.01 mg to 100 mg. For example, the topical composition may be administered in doses of approximately 1 mg to 30 mg, 20 mg to 40 mg, 30 mg to 50 mg, 40 mg to 60 mg, 50 mg to 100 mg, 80 mg to 100 mg, 60 mg to 100 mg, 10 mg to 40 mg, 20 mg to 60 mg, 30 mg to 70 mg, 40 mg to 80 mg, 50 mg to 90 mg, 60 mg to 100 mg, 70 mg to 100 mg, greater than 10 mg, greater than 25 mg, greater than 50 mg, or greater than 75 mg. In one example, the above dosage may be administered once or twice a day, in multiple divided doses per day, every other day, twice a week, or by any other method deemed appropriate.

[0054] In one embodiment, the topical composition may be administered orally or via other transmucosal routes for oral absorption in effective doses of about 0.1 mg to about 1 mg, about 0.1 mg to about 0.8 mg, about 0.1 mg to about 0.6 mg, about 0.1 mg to about 0.6 mg, about 0.25 mg to about 0.5 mg, or about 0.5 mg to about 1 mg. In some embodiments, the dose for some GLP-1 receptor agonists, such as exenatide or lixisenatide, may be less than 0.01 mg. For example, the dose may be about 0.001 mg to 0.01 mg, e.g., about 0.003 mg to about 0.01 mg, or about 0.005 mg to about 0.01 mg. Such doses may be effective for once-daily or twice-daily administration via transmucosal administration. Higher doses may be deemed suitable for transmucosal or transdermal administration. For example, topical compositions may be administered in doses of approximately 1 mg to 20 mg, such as 1 mg to approximately 5 mg, approximately 1 mg to approximately 10 mg, approximately 1 mg to approximately 15 mg, approximately 2 mg to approximately 6 mg, approximately 3 mg to approximately 10 mg, approximately 4 mg to approximately 15 mg, approximately 6 mg to approximately 15 mg, approximately 10 mg to approximately 20 mg, approximately 10 mg to approximately 15 mg, or approximately 15 mg to approximately 20 mg.

[0055] Topical compositions may be supplied at any appropriate concentration. The appropriate concentration may be determined by those skilled in the art based on this disclosure. In various applications, the selection of concentration may take into account the desired dose, volume / weight, route of administration, or other considerations. For example, a higher concentration may be appropriate for lower doses. In one example, the concentration of a GLP-1 receptor agonist, such as semaglutide, in a topical composition may be approximately 0.001% to approximately 10% (w / v). For example, topical compositions prepared for transmucosal administration may be supplied at concentrations of approximately 0.001% to 0.01%, 0.001% to 0.1%, 0.05% to 1%, 0.05% to 0.5%, 0.08% to 0.2%, 0.08% to 0.15%, 0.075% to 0.125%, 0.01% to 0.1%, 0.1% to 1%, 1% to 2%, 2% to 5%, 4% to 8%, greater than 0.08%, less than 0.5%, less than 0.3%, or less than 1.5%. Higher or lower concentrations may also be used. Compositions for transdermal administration may be supplied at concentrations similar to those for transmucosal administration. In one embodiment, the topical composition comprises a suspension provided at approximately 0.5 mg / mL, approximately 1 mg / mL, approximately 1.5 mg / mL, approximately 2 mg / mL, approximately 2.5 mg / mL, approximately 3 mg / mL, approximately 4 mg / mL, approximately 6 mg / mL, approximately 10 mg / mL, approximately 50 mg / mL, or approximately 100 mg / mL.

[0056] In one dosage form, the topical composition may be in the form of a dry powder. The powder may be compressed into a powder, encapsulated, or tablet form for oral administration, for example, an intraoral tablet or a sublingual tablet. The powder may be placed under the tongue, on the gums and / or in the cheek (e.g., in the oral pouch), and all or part of the powder contents may be dissolved, wet, hydrated, solubilized, or reconstituted by saliva in situ and absorbed by the mucous membrane. For example, in a preliposome dosage form, the powder may be reconstituted in situ to form liposomes, which are delivered by oral absorption. In one embodiment, the powder may be provided filled in a pouch for oral administration. In one embodiment, the powder may be provided filled in a capsule containing a liquid separate from the powder. The capsule may be mechanically crushed or dissolved in biological fluids, and the powder and liquid may be mixed in situ. In various embodiments, the topical composition comprises a powder base. In these or other embodiments, the topical composition comprises one or more surfactants, pH adjusters, fragrances, viscosity modifiers, preservatives, etc.

[0057] In various embodiments, the powder may contain particle sizes ranging from extremely fine particles to fine particles, for example, less than about 50 microns, less than about 40 microns, less than about 30 microns, less than about 25 microns, or less than about 20 microns. In some examples, the particle size represents the average or majority of particles within the range, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 98%. In further examples, the particles remaining outside the particle size range may be up to about 25%, about 20%, about 15%, about 10%, or about 5% larger.

[0058] As detailed below, in some embodiments, powder dosage forms may be administered topically to the skin, mucous membranes, or both. In further embodiments, topical compositions may be prepared from powders or powder mixtures mixed with a base. The base may consist of a solution (e.g., aqueous, anhydrous), a colloidal suspension (e.g., emulsion, anhydrous suspension), an oil, an ointment, a cream, a lotion, a paste, a gel, or other base suitable for topical administration.

[0059] Topical compositions comprising powder for administration in powder form, or powder for mixing with a non-powdered base, may contain one or more additional components such as xylitol, poloxamer, sodium salcaprozate, sodium caprate, lactose, starch, magnesium stearate, cellulose or cellulose derivatives, microcrystalline cellulose, sugars, sugar alcohols, povidone, talc, or combinations thereof. In embodiments comprising a liquid or semi-liquid base, or prepared to be mixed with a liquid or semi-liquid base, the powder, base, or other topical composition may contain one or more additional components such as xylitol, poloxamer, sodium salcaprozate, sodium caprate, lactose, starch, magnesium stearate, cellulose or cellulose derivatives, microcrystalline cellulose, sugars, sugar alcohols, povidone, talc, or combinations thereof. In some embodiments, the additional components in the topical composition may include a sodium-glucose cotransporter 2 inhibitor. For example, sodium-glucose cotransporter 2 inhibitors may be selected from one or more of the following: canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin.

[0060] As described above, in some embodiments, the topical composition comprises liposomes or mixed micelle delivery systems. In one example, the topical composition comprises a powder mixture of preliposomes and semaglutide. In further examples, the preliposome powder mixture may contain one or more additional components such as xylitol, poloxamer, sodium salcaprozate, sodium caprate, lactose, starch, magnesium stearate, cellulose or cellulose derivatives, microcrystalline cellulose, sugars, sugar alcohols, povidone, talc, or combinations thereof. The preliposome powder may contain or be mixed with a powder or liquid of the GLP-1 receptor. The preliposome powder may be reconstituted before administration. For example, the preliposome powder may be prepared to be reconstituted in a liquid medium to prepare a solution or suspension. The liquid medium may include, for example, an aqueous medium, anhydrous medium, emulsion, oil, water, or other medium suitable for topical administration to the oral cavity or other desired body surface. In one example, the preliposome powder may contain or be mixed with a powder or liquid of the GLP-1 receptor. The mixture may be further mixed with an anhydrous medium before administration, which may be minutes, hours, days, or months before administration.

[0061] In some embodiments, preliposome powders may be prepared to be reconstituted in situ. For example, topical composition powders may be administered to the skin or a mucous membrane surface such as the oral cavity to be reconstituted by interaction with body fluids. For example, a topical composition may be a powder for administration into the nasal cavity. Upon administration, the topical composition may be deposited along the nasal mucosa of the nostrils. Upon administration, the topical composition may be deposited along the mucosa of the paranasal sinuses. In one example, the topical composition comprises preliposomes configured for liposome delivery by reconstitution with body fluids, as described herein. As described above, powdery dosage forms may include tablets, capsules, or powders. In one example, preliposome powder may be dispersed in oral lozenges, oral tablets, sublingual tablets, or encapsulated in pouches to be orally absorbed by reconstitution in situ. In some embodiments, the powder or base medium may contain one or more flavorings and / or sweeteners as described herein. In some embodiments, a topical composition containing preliposome powder may be mixed with a base medium to prepare a suspension, cream, lotion, ointment, gel, or paste for topical administration via mucosal or transdermal administration.

[0062] In various embodiments, topical compositions may be provided in liquid dosage forms. These liquid dosage forms may include an anhydrous lipid suspension containing a GLP-1 receptor agonist suspended in a lipid carrier containing phospholipids. Such suspensions may include liposome systems or mixed micelle systems. In one example, the liposome system or mixed micelle system is referred to as a pre-liposome, prepared to form a liposome system or mixed micelle system upon addition of an aqueous liquid or when placed in an aqueous environment. In further examples, the pre-liposome and base carrier include self-emulsifying liposomes upon addition of an aqueous liquid or when placed in an aqueous environment.

[0063] In one embodiment, the topical composition comprises a suspension. The suspension may be administered orally for oral absorption. In one example, the suspension may be prepared immediately before administration by mixing the components of the topical composition with a liquid base which may contain one or more of its components. In another example, the suspension may be prepared several days, weeks, or months before administration. Thus, the suspension may be stable for a long period of time. In one example, the suspension comprises an anhydrous base. The base may contain oils, or it may contain an oil mixture. The base may contain a lipid-based drug delivery system. In one dosage form, the base comprises an emulsion. The base may be a buffered suspension base, a syrup, an elixir, etc. The suspension may contain various additives, such as surfactants, penetration enhancers, chelating agents, pH adjusters, flavorings and / or sweeteners, viscosity modifiers, preservatives, release agents (e.g., sustained-release, controlled-release, delayed-release, or extended-release), and absorption modifiers. In one example, one or more additives include xylitol, poloxamer, sodium salcaprozate, sodium caprate, lactose, starch, magnesium stearate, cellulose or cellulose derivatives, microcrystalline cellulose, sugars, sugar alcohols, povidone, talc, or a combination thereof. In one example, the topical composition does not contain preservatives. In one embodiment, the topical composition includes semaglutide suspended in an anhydrous base containing lipids in a preliposome dosage form. In various embodiments, the topical composition includes one or more penetration enhancers to facilitate delivery and permeation to the buccal mucosa or gingival tissue. In one example, the topical composition or base includes diethylene glycol monoethyl ether NF.

[0064] As described above, in various embodiments, the topical composition comprises a liposome system or a mixed micelle system. For example, the topical composition may comprise a liposome base suspension encapsulating or associating a GLP-1 receptor agonist such as semaglutide. In further examples, the liposomes may encapsulate or associate the GLP-1 receptor agonist with one or more additional components. The topical composition may comprise mixed micelles. The mixed micelles may encapsulate or associate the GLP-1 receptor agonist. One or more additional components may include xylitol, poloxamer, sodium salcaprozate, sodium caprate, lactose, starch, magnesium stearate, cellulose or cellulose derivatives, microcrystalline cellulose, sugars, sugar alcohols, povidone, talc, or combinations thereof. In further examples, the liposome-containing medium may contain one or more additional components, which may be added to or replaced with those encapsulated in the liposome delivery base. For example, xylitol, poloxamer, or both may be contained in the liposome-containing medium, and the GLP-1 receptor agonist may be encapsulated alone or with one or more additional components selected from sodium salcaprozate, sodium caprate, lactose, starch, magnesium stearate, cellulose or cellulose derivatives, microcrystalline cellulose, sugars, sugar alcohols, povidone, talc, or combinations thereof. In some embodiments, the additional components may include sodium-glucose cotransporter 2 inhibitors, such as those selected from one or more of canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin.

[0065] In various embodiments, the liposome system or mixed micelle system comprises liposomes and / or micelles in an anhydrous medium, which may be in the form of preliposomes or other lipid-based forms prior to the initiation of exposure to the aqueous medium. In another example, the base comprises liposomes and / or micelles in an emulsion. In one example, the topical composition comprises an anhydrous liposome or micelle base suspension containing semaglutide encapsulated, associated, or present. In some embodiments, the suspension is prepared by mixing preliposome powder, semaglutide, and a liquid base, which may be done immediately before or immediately after administration. In one embodiment, the liposome system or mixed micelle system comprises an anhydrous liquid base, which comprises lipids such as phospholipids, oils, or both. The anhydrous liquid base may have a preliposome dosage form configured to self-emulsify as described herein. In other dosage forms, the liquid base comprises an aqueous base. In some embodiments, the suspension is prepared by mixing a GLP-1 receptor agonist, such as semaglutide, with the base. The base may be an anhydrous liquid containing phospholipids. The base may be configured to self-emulsify in an aqueous environment, which may be an aqueous biological fluid, an aqueous liquid added to or replenished at the administration site, or an in-situ environment driven by an aqueous liquid added to the administration site before administration.

[0066] Topical compositions containing liposomes or mixed micelles may be prepared for oral absorption, for example, sublingually, buccally, or otherwise. Topical compositions containing liposomes or mixed micelles may be prepared for transmucosal administration to the rectum, nasal cavity, or vagina. Topical compositions containing liposomes or mixed micelles may be prepared for transdermal administration to the skin surface. In some embodiments, topical compositions containing liposomes or mixed micelles include suspensions, ointments, creams, lotions, gels, pastes, or solutions.

[0067] In various embodiments, the topical composition contains one or more penetration-enhancing components. These components may be contained in or added to the bases described herein. The penetration-enhancing components may be included to promote delivery and penetration into the buccal mucosa or gingival tissue. For example, the penetration-enhancing component may include diethylene glycol monoethyl ether NF (Transcutol HP). In some embodiments, the penetration-enhancing component is selected to also have emulsifying or surfactant properties to impart self-emulsifying properties to the topical composition. The penetration-enhancing component may be included in compositions comprising liposomes or mixed micelles.

[0068] In various embodiments, topical compositions configured for oral absorption include one or more fragrances and / or sweeteners. For example, the fragrances and / or sweeteners may be provided in powder composition dosage forms (powder, pouch, tablet, capsule, etc.), suspension composition dosage forms, solution composition dosage forms, lozenge composition dosage forms, or other dosage forms for oral absorption. The fragrances may be natural, artificial, synthetic, or a combination thereof. The sweeteners may consist of one or more artificial, synthetic, or natural sweeteners. In one example, the sweeteners include monk fruit (Siraitia grosvenori). In this example or another, the sweeteners include sucralose. The fragrances may include methyl salicylate, one or more natural essential oils, or a combination thereof. The fragrances may include natural or synthetic essential oils. The essential oils may include, for example, lemon, peppermint, lavender, or rose. Flavorings may include, or may be derived from, flavoring powders such as banana, chocolate, strawberry, vanilla, pineapple, mango, or other suitable flavoring powders. Examples of flavorings may include bitter flavorings such as chocolate, peanut oil, olive oil, walnut, almond, wild cherry, sesame oil, corn oil, mint, anise, monk fruit, marshmallow oil, or combinations thereof. Flavorings may include cherry, grape, raspberry, peppermint, cinnamon, peach, orange, mixed fruit, apricot, honey, butterscotch, clove, ginger, ethyl maltol, cardamom, capric acid, malic acid, ethyl acetate, methionine, maltol, spearmint, menthol, or combinations thereof.

[0069] In various embodiments, topical compositions prepared for oral absorption may be mixed with an aqueous solution such as water or juice before administration. For example, the powders, aqueous suspensions, colloidal suspensions, or anhydrous suspensions described above and elsewhere in this specification may be mixed with an aqueous solution such as water or juice before administration, and the mixing may occur immediately before administration, for example, within one hour, or may be allowed for a longer period in the case of stable dosage forms. In one example, a topical composition comprising a self-emulsifying anhydrous base may be configured to be mixed with an aqueous liquid before administration. The self-emulsifying anhydrous base may comprise an anhydrous liquid or powder. The self-emulsifying anhydrous base may comprise a lipid-based delivery system. The self-emulsifying anhydrous base may comprise liposome systems and / or mixed micelle systems prepared to form self-emulsifying liposomes in an aqueous environment or upon addition of an aqueous liquid.

[0070] As described above, topical compositions may be prepared for transmucosal and / or transdermal delivery by application to the skin or the mucous membranes of the oral cavity, nasal cavity, vagina, or rectum. In various embodiments, topical compositions are provided in dosage forms selected from colloids or emulsions (o / w, w / o), creams, lotions, ointments, foams, aqueous or non-aqueous gels, aqueous or non-aqueous solutions or suspensions, anhydrous suspensions, dispersions, pastes, or powders. Powder dosage forms include those described above and elsewhere in this specification, and include powders, oral tablets, sublingual tablets, capsules, pouches, lozenges, and suppositories. Also, as described above, various embodiments of topical compositions may be prepared by mixing a powder containing a GLP-1 receptor agonist with a base to prepare a composition having a desired dosage form. Additional components, as described herein, may be present as powders, bases, or in mixtures thereof.

[0071] The base may be liquid, semi-liquid, or solid. For example, the base may include aqueous solutions, aqueous solutions, organic solutions, or inorganic solutions, and may include dispersions, suspensions, creams, gels, ointments, lotions, emulsions, powders, or pastes. In some embodiments, the base includes a base cream, ointment, gel, lotion, foam, or solution. The base may include base components such as lecithin, phospholipids, glycols, paraffin, fatty acids, carbopole / carbomer, alcohols, or lanolin.

[0072] In some embodiments, the base includes an aqueous solution. In some examples, the base including an aqueous solution may be mixed with components of a topical composition to prepare the topical composition. In one embodiment, the base or its components may include an aqueous solution containing physiological saline. For example, the topical composition may include a base or component containing a sodium hydroxide solution, which may be a sterile solution, or a base or component containing alcohol, water, e.g., purified water, perfusion water, water for injection, or sterile water. In one embodiment, the base or its components include a 0.09% sodium chloride solution (sterile). The base or its components may be present in an amount sufficient to obtain the desired amount of active ingredient per unit weight or unit volume.

[0073] In some embodiments, the topical composition may contain a base component including polyethylene glycol (PEG) as a base component. In other embodiments, the topical composition does not contain PEG. In these or other embodiments, the topical composition may contain a silicone base component or a silicone derivative base component. In some embodiments, the topical composition does not contain silicone. Examples of compositions may include solutions containing a base component selected from water, alcohol, DMSO, saline solution, or sodium chloride, sodium hypochlorite, or other aqueous or anhydrous base media, in which one or more components of the topical composition are mixed, dispersed, suspended, solubilized, or dissolved. The topical composition may be prepared to be water-soluble / miscible or water-absorbent. The topical composition may include a water-in-oil emulsion or an oil-in-water emulsion. In one embodiment, the topical composition comprises, for example, an emulsion in the form of a cream or lotion, the emulsion comprising one or more base components selected from acrylate copolymers, alcohols, camphor, carbomer, dimethyl isosorbide, disodium EDTA, dl-α-tocopheryl acetate, disodium edetate, emulsifying wax, eucalyptus oil, flavonoids, glycerin, dicaprylic / glycol dicaprate, hydroxyethylcellulose, isopropyl myristate, lactic acid, meadowsweet extract, menthol, mineral oil, neopentyl, phenolic glycosides, polyethylene glycol (PEG), polysorbate (e.g., polysorbate 85, polysorbate 20), purified water, titanium dioxide, tridecyl stearate, tridecyl trimellitic acid, sodium hydroxide, sodium hydroxide, sorbitol, stearic acid, zinc pyrition, or combinations thereof. In some embodiments, the topical composition has a foam dosage form comprising a propellant base component such as butane. Compositions in foam formulation may also have additional properties such as being an emulsion, such as an oil-in-water emulsion, or a gel.

[0074] In one example, the topical composition has an ointment dosage form containing a base component selected from hydrophilic petrolatum, white petrolatum, hydrophilic ointment, white ointment, anhydrous lanolin, hydrated lanolin, PEG ointment, or a combination thereof. In one embodiment, the topical composition has a gel dosage form. The gel may be an aqueous gel or an anhydrous gel. The gel may contain a base component containing a thickener and / or gelling agent such as carbopol, poloxamer, xanthan gum, methylcellulose, carboxymethylcellulose, hydroxyethylcellulose, ethylcellulose, gelatin, magnesium aluminum silicate, polyvinyl alcohol, sodium alginate, or a combination thereof.

[0075] The topical composition or its base may contain one or more base components such as solubilizers, stabilizers, buffers, osmotic pressure regulators, bulking agents, viscosity improvers / decreasers, surfactants, chelating agents, auxiliary agents, or combinations thereof.

[0076] In various embodiments, the topical composition or its base comprises one or more glucose polymers, such as starch, cellulose or cellulose derivatives, polydextrose, or combinations thereof. Examples of starch may include sodium starch glycolate, comb starch, pre-gelatinized starch, or combinations thereof. Examples of cellulose may include hydroxypropyl cellulose, hypermellose, croscarmellose sodium, ethyl cellulose, microcrystalline cellulose, or combinations thereof. Povidones, such as povidone K30, copovidone, crospovidone, or combinations thereof, may also be present. In some embodiments, glycols and / or sugar alcohols may be present. Examples of glycols may include polyethylene glycol, propylene glycol, or combinations thereof. Examples of sugar alcohols may include mannitol. Some embodiments may contain oxides, such as silicon dioxide, titanium dioxide, iron oxide, or combinations thereof. One embodiment may include any of the above, along with magnesium stearate, talc, diethyl phthalate, sodium stearate fumarate, sodium lauryl sulfate, polysorbate, triacetin, polaricrin, lactose, glycerol behenate, polyvinyl alcohol, carnauba wax, or a combination thereof. In one embodiment, the topical composition does not contain one or more of the following: starch, cellulose, polydextrose, sodium starch glycolate, corn starch, pre-gelatinized starch, hydroxypropylcellulose, hypermellose, croscarmellose sodium, ethylcellulose, microcrystalline cellulose, povidone, povidone K30, copovidone, crospovidone, polyethylene glycol, propylene glycol, mannitol, silicon dioxide, titanium dioxide, iron oxide, magnesium stearate, talc, diethyl phthalate, sodium stearyl fumarate, sodium lauryl sulfate, polysorbate, triacetin, polarin, lactose, glycerol behenate, polyvinyl alcohol, carnauba wax, or any combination thereof.

[0077] In some embodiments, the base comprises a water-washable moisturizing ointment containing polyethylene glycol, water, chickweed flower extract, zinc acetate, and propylene glycol. In one embodiment, the polyethylene glycol comprises PEG-8 and PEG-75.

[0078] In various embodiments, the topical composition is anhydrous and contains a GLP-1 receptor agonist in the anhydrous base. In one example, the GLP-1 receptor agonist is semaglutide. The topical composition may be prepared to self-emulsify in an aqueous environment. For example, the topical composition may contain a component that confers self-emulsifying ability to the topical composition in an aqueous environment. In some embodiments, the aqueous environment is the administration site, and the topical composition self-emulsifies in situ. The aqueous environment may be provided by a biological fluid. For example, oral administration exposes the topical composition to saliva, thereby promoting self-emulsification. In some embodiments, self-emulsification promotes the formation of liposomes and / or mixed micelles for transmucosal or transdermal administration.

[0079] In some embodiments, the topical composition comprises medium-chain triglyceride NF, glycerin USP, glyceryl distearate NF, stearoyl polyoxyl-32 glyceride NF, ascorbyl palmitate NF, vitamin E acetate USP, and monk fruit extract of Silatia grosvenorii, and a GLP-1 receptor agonist. In one example, the GLP-1 receptor agonist is semaglutide. For example, an anhydrous self-emulsifying base may contain medium-chain triglyceride NF, glycerin USP, glyceryl distearate NF, stearoyl polyoxyl-32 glyceride NF, ascorbyl palmitate NF, and vitamin E acetate USP. Flavorings and / or sweeteners as described herein may be included in or added to the topical composition. In lipid-based dosage forms, the topical composition may further contain a nonionic water-dispersible surfactant to solubilize poorly water-soluble active ingredients and improve oral bioavailability. Local compositions may self-emulsify in aqueous media to form fine dispersions, which are sometimes called microemulsions (SMEDDS).

[0080] In one example, a topical composition may be prepared in a base configured to spontaneously form self-emulsifying liposomes, which may contain micelles or mixed micelles, in order to improve drug delivery. For example, a topical composition may include an aqueous liquid, for example, a self-emulsifying liposome dosage form designed to form an emulsion upon contact with saliva in sublingual administration. A topical composition may be anhydrous and self-emulsify in an aqueous environment. A topical composition may be prepared to self-emulsify in situ. For example, administration of a topical composition into a subject's oral cavity may cause the topical composition to self-emulsify upon interaction with saliva. This process may occur without the addition of mechanical or thermal energy. In various embodiments, the anhydrous self-emulsifying base includes a self-emulsifying liposome base containing phosphatidylcholine and lysophosphatidylcholine. For example, the base may contain a synergistic combination of approximately 0.5 w / w% to approximately 10 w / w%, preferably approximately 3 w / w%, of phosphatidylcholine and approximately 0.1 w / w% to approximately 1 w / w%, preferably approximately 0.36 w / w%, of lysophosphatidylcholine.

[0081] In some embodiments, the base comprises an anhydrous lipid base configured to self-emulsify in an aqueous environment. In one example, the base may contain caprylic / capric triglyceride. In this or another example, the base comprises glyceryl stearate, such as glyceryl monostearate, glyceryl distearate, or both. In either or another example, the base comprises phosphatidylcholine, lysophosphatidylcholine, polycarbophil, glyceryl distearate, and glyceryl monostearate. In either or another example above, the base may contain fragrances and / or sweeteners as described herein, such as monk fruit, natural oil fragrances, sucralose, or combinations thereof. The dosage form of the topical composition may comprise a mixed powder containing a GLP-1 receptor agonist and the base. The base may be pre-formulated before mixing, or one or more components may be further mixed. For example, one or more flavorings or sweeteners may be added before or after mixing the powder with other components of the base.

[0082] In various embodiments, the topical composition contains polycarbophil. Polycarbophil can improve the topical composition by achieving both extended contact time and effective bitterness masking. Extended contact time and effective bitterness masking may position the topical composition as an optimal choice for sublingual drug delivery.

[0083] Additionally or alternatively, topical compositions may incorporate special techniques designed to counteract the bitterness often associated with drugs such as semaglutides. For example, topical compositions may employ unique film-forming adhesion techniques combining glyceryl distearate, glyceryl monostearate, and polycarbophil. The combination works synergistically to reduce bitterness by forming a protective film that minimizes initial direct contact of the drug with the taste buds. If necessary, sweeteners and / or flavorings may be added to further reduce residual bitterness during administration. Examples of sweeteners and flavorings may include those described herein, such as marshmallow oil flavoring, sucralose, monk fruit (Siraitia grosvenori), or combinations thereof.

[0084] In one embodiment, the topical composition utilizes the synergistic effect of glyceryl distearate, glyceryl monostearate, and polycarbophil. For example, when administered sublingually, these components work together to form a protective matrix. This matrix adheres firmly to the sublingual mucosa, thereby extending the contact time of the dosage form with the mucosal surface. The extension of contact time, primarily facilitated by polycarbophil, enhances the absorption of the active ingredient through the sublingual pathway, leading to improved bioavailability and optimized therapeutic effect. Simultaneously, glyceryl distearate and glyceryl monostearate form an anhydrous film, not only improving drug contact time but also minimizing drug interaction with taste buds and reducing bitterness. The combination of polycarbophil, glyceryl distearate, and glyceryl monostearate also acts as an effective bitterness reducer, skillfully masking the bitterness of certain active ingredients.

[0085] Table 1 shows examples of bases for compounding GLP-1 receptor agonists to produce self-emulsifying suspensions. The suspensions may be anhydrous, or they may be configured to self-emulsify in an aqueous environment, for example, provided in situ by the body fluids of the administration site. The bases in Table 1 are also prepared for taste masking and adhesion, as described above.

[0086] [Table 1]

[0087] The active ingredient, phosal 53MCT, contains at least 53% phosphatidylcholine and at most 6% lysophosphatidylcholine. In some embodiments, the base contains a synergistic combination of about 0.5 w / w% to about 10 w / w% phosphatidylcholine and about 0.1 w / w% to about 1 w / w% lysophosphatidylcholine. The currently preferred dosage form contains about 3 w / w% phosphatidylcholine and about 0.36 w / w% lysophosphatidylcholine. As described above and elsewhere in this specification, fragrances are optional and may be added separately. One or more ingredients may be omitted or replaced with medicinal ingredients deemed equivalent.

[0088] Table 2 shows an example of a preparation procedure for preparing a topical composition containing a semaglutide suspension. As shown, the base includes a self-emulsifying liposome suspension (Table 1), but other bases described herein may also be used. The procedure involves mixing a crushed commercially available oral semaglutide tablet (RYBELSSU® 14 mg) with the base (Table 1). The tablet was crushed separately. Each component was weighed using a suitable balance. Each component was compounded in an electric mortar and mixed once on standard in an Ungator 2100. The viscosity is preferably in the range of 100 to 1500 CPS, but depends on the presence or absence of humectants and oily fragrances.

[0089] [Table 2]

[0090] The preparation of a topical composition may involve mixing a powder containing a GLP-1 receptor agonist with a medium sometimes called a base. The base may be a liquid anhydrous containing lipids. The base may be a liquid anhydrous base containing phosphatidylcholine and lysophosphatidylcholine. The base may additionally or alternatively contain polycarbophil. The base may additionally or alternatively contain glyceryl distearate and glyceryl monostearate. The base may be self-emulsifying as described herein. The base may consist of bases listed in Table 1 or elsewhere in this specification. To prepare a topical composition, the user may grind the powder. The powder may be moistened with a wetting agent as needed. Examples of wetting agents include propylene glycol or glycerin. Adding and mixing the base improves the solubility of the topical composition in the lipid suspension. Sublingual administration spontaneously forms self-emulsifying liposomes, improving drug delivery. For more refined pre-liposome formation, an electric mortar may be used. This device allows for more uniform and thorough mixing, ensuring the highest quality of the final product.

[0091] In various embodiments, topical compositions may be administered topically by contact with external surfaces of the body, which may include the skin, vaginal orifice, and anal orifice for absorption. Topical compositions may be administered orally or nasally for absorption. Topical compositions may be administered in dosage forms suitable for topical administration, such as sprays, ointments, dipping, powders, and powders.

[0092] Methods for preparing topical compositions may involve obtaining all or part of a GLP-1 receptor agonist, alone or with one or more additional components, from a powder dosage form, such as bulk powder, crushed tablets, injectable powder, or other commercially available composition. The powder may be mixed with a base, such as those described herein. The method may involve compounding the base with the powder containing all or part of the GLP-1 receptor agonist. For example, the GLP-1 receptor agonist may be obtained by crushing and / or powdering commercially available tablets to a desired particle size. In one embodiment, all or part of the GLP-1 receptor agonist may be obtained from a commercially available injectable powder or solution and mixed with a base to prepare a topical composition. In one example, the GLP-1 receptor powder is moistened before being mixed with the base. For example, according to various preparation methods, the powder may be moistened with DMSO, alcohol, or water. In one embodiment, the powder may be moistened with propylene glycol or glycerin. According to one method, all or part of the additional components may be provided in a dosage form selected from solutions, emulsions, gels, creams, lotions, ointments, or other dosage forms, and may be formulated with a base and all or part of the GLP-1 receptor agonist, or separately from all or part of the GLP-1 receptor agonist. In one example, all or part of the additional components may be mixed with all or part of the GLP-1 receptor agonist before being mixed with other components of the base. In another example, the GLP-1 receptor agonist is added to an additional component contained in a commercially available medicinal composition containing a base. The base may include a commercially available base containing one or more additional components, and a powder or other dosage form containing the GLP-1 receptor agonist may be mixed therein for the preparation of a topical composition. For example, a suspension base containing a fragrance may be mixed with the GLP-1 receptor agonist for oral administration by oral absorption. In one example, the GLP-1 receptor agonist is obtained from the crushing of commercially available oral tablets for oral administration. The powder may be mixed with a base containing phospholipids and / or preliposomes for subsequent reconstitution with liquid base components.The powder may be mixed with a phospholipid base to prepare a liposome system or a mixed micelle system. In one example, the powder is mixed with a suspension base containing a liposome system or a mixed micelle system. In one dosage form, the base is an anhydrous liquid. The base may be a liquid anhydrous containing lipids. The base may be a liquid anhydrous base containing phosphatidylcholine and lysophosphatidylcholine. The base may additionally or alternatively contain polycarbophil, glyceryl distearate, and glyceryl monostearate. The base may be self-emulsifying as described herein. In further examples, the base may contain or have added fragrances as needed. The base may consist of the bases described in Table 1 or elsewhere in this specification.

[0093] In some embodiments, topical compositions containing anhydrous self-emulsifying compositions may be compounded with an aqueous liquid before administration to promote emulsification. In one embodiment, emulsification may result in the formation of a microemulsion. In one embodiment, emulsification may result in the formation of a liposome system or a mixed micelle system.

[0094] The number of tablets used in preparing a GLP-1 receptor agonist to prepare a topical composition containing a desired weight of the GLP-1 receptor agonist may be determined by dividing the required weight of the GLP-1 receptor agonist by the weight of the GLP-1 receptor agonist in the tablets. The weight of tablet powder required to prepare a composition containing a desired weight of the GLP-1 receptor agonist may be determined by dividing the weight of the tablets by the weight of the GLP-1 receptor agonist present in the tablets and multiplying the result by the weight of the desired GLP-1 receptor agonist in the topical composition.

[0095] In one embodiment, the method for preparing a topical composition includes crushing a commercially available oral tablet of a GLP-1 receptor agonist, or obtaining a powder from a crushed commercially available oral tablet of a GLP-1 receptor agonist. In one example, the topical composition is prepared from a commercially available semaglutide oral tablet. The tablet may preferably be powdered separately from the base. Dosage forms of any desired concentration may be prepared according to the description of the present invention. For example, the oral tablet may be weighed to determine the amount of semaglutide per unit volume. This formula is then used to determine the amount of tablet powder required to blend the base and any additional components to obtain a composition of the desired percentage. For example, a 14 mg RYBELSUS® tablet has an average weight of 0.409 g. To prepare a 1 mg / ml semaglutide composition using the powder of a 14 mg semaglutide oral tablet, 1 ml of the topical composition contains 1 mg of semaglutide, which is 1 / 14 of one tablet, or 7.14%. Therefore, 1 ml of the topical composition contains 29.214 mg of the tablet powder, and the desired concentration may be obtained by mixing the powder with the base and any other components to a volume equivalent to the weight of the tablet powder of the desired concentration. A suitable amount of powder containing the desired amount of semaglutide may be mixed with the desired base. The base may be any base described herein. For example, the base may be aqueous, non-aqueous, anhydrous, emulsion, liquid, semi-solid, or solid. By mixing the base with the ground semaglutide tablet powder, powders, solutions, suspensions, ointments, creams, gels, or pastes can be prepared. In one embodiment, the resulting powder may be compressed into tablet dosage forms or encapsulated in capsules or pouches for oral administration via oral, sublingual, or other oral absorption delivery. In one embodiment, the mixture may be completely or partially solidified to produce a gel or oral absorption lozenge. In one embodiment, the base includes an anhydrous suspension base. In further embodiments, the base comprises an anhydrous suspension base containing liposomes.As described herein, liposomes may be present in a mixed micelle system or may be provided purely, such as in a system containing aggregated lipids associated primarily or substantially in a bilayer. In one embodiment, the base comprises a mixed micelle system that does not contain liposomes. In one example dosage form, the suspension base is prepared to self-emulsify in an aqueous environment. In one embodiment, the base comprises an anhydrous suspension base and is mixed with a powder containing pulverized semaglutide tablets and preliposomes. In one embodiment, the anhydrous suspension base or powder contains mixed micelles, with or without preliposomes. The base, powder, or mixture may contain additional components, such as those described herein, or may be formulated with additional components. In one example, the additional components may include flavorings and / or sweeteners. For example, the flavorings may include sweeteners to mask the bitterness of semaglutide, other GLP-1 receptor agonists, or other activators. In one embodiment, the flavorings and / or sweeteners may be added to the pulverized tablet powder. For example, the preparation of a topical composition may involve grinding a fragrance, such as a sweetener powder, with a pulverized tablet powder and then mixing it with a base, which may be an anhydrous substance. In one embodiment, the fragrance may be embedded in the base. For example, the fragrance, such as a sweetener powder, may be embedded in the base, and the preparation of the topical composition may involve compounding the pulverized tablet powder with the base. In some embodiments, the fragrance may be provided as a liquid. In one example, the fragrance may be used to moisten the pulverized tablet powder.

[0096] This disclosure describes various embodiments of compositions comprising semaglutide. However, it is understood that these embodiments may additionally or alternatively contain other GLP-1 receptor agonists such as liraglutide, exenatide, lixisenatide, taspoglutide, rotiglypron, dulaglutide, tylzepatide, albiglutide, danuglypron, orfolglipron, efpeglenatide, or combinations thereof. Accordingly, all various embodiments comprising semaglutide are disclosed additionally or alternatively as containing one or more GLP-1 receptor agonists. GLP-1 receptor agonists may contain one or more of the following GLP-1 receptor agonists, either alone or in combination: semaglutide, liraglutide, exenatide, lixisenatide, taspoglutide, rotiglypron, dulaglutide, tylzepatide, albiglutide, danuglypron, orfolglypron, efpeglenatide, or other GLP-1 receptor agonists. Compounds, active ingredients, and other components described herein are understood to include derivatives, analogues, and pharmaceutically acceptable equivalents unless otherwise specified. The bases described herein may refer to the excipient portion of a topical composition and not necessarily to the group of components added before the activator. In fact, the components of a base may be combined with the base (other components) in any order suitable for the preparation of the topical composition. For example, if present, fragrances and / or sweeteners may be formulated with the active ingredient, other base ingredients, or a combination thereof, either alone or in any order, to simultaneously achieve the functions of the fragrance and / or sweetener and the functions of the topical composition.

[0097] Embodiments described herein that contain a self-emulsifying base or are prepared to self-emulsify in an aqueous environment may be administered topically as described herein. For example, topical compositions may be administered transdermally or transmucosally. Topical compositions may be administered orally, anally, rectally, nasally, in the ear, or vaginally.

[0098] Topical compositions containing anhydrous self-emulsifying bases are not only advantageous for sublingual administration, but their self-emulsifying liposome properties also make them highly versatile and usable in other sites. Therefore, topical compositions are suitable not only for oral administration, but also for intranasal, oral, vaginal, topical, and even hair care formulations. Their multifunctional design offers the possibility of a wide range of drug delivery and care solutions, beyond just the delivery of GLP-1 receptor agonists. In fact, those skilled in the art will understand from reading this specification that embodiments described herein, containing a self-emulsifying base or prepared to self-emulsify in an aqueous environment, may contain one or more activators in addition to, or instead of, one or more GLP-1 receptor agonists. Examples of non-limiting active ingredients may be selected from analgesics, androgen hormones, antacids, anxiolytics, antiarrhythmics, antibacterial agents, antibiotics, anticoagulants, antidepressants, antidiarrheals, antiemetics, antifungals, antihistamines, antihypertensives, anti-inflammatory agents, anticancer agents, antipsychotics, antipyretics, antivirals, anxiolytics, barbiturates, beta-blockers, bronchodilators, cold medicines, corticosteroids, antitussives, cytotoxic agents, nasal congestion relievers, diuretics, expectorants, hormones, hypoglycemic agents, immunosuppressants, laxatives, mucolytics, muscle relaxants, sedatives, hypnotics, thrombolytics, tranquilizers, or vitamins. Such topical compositions may be administered to treat diseases for which such activators have been used in the treatment of this field. Such topical compositions may be administered topically for transdermal or transmucosal delivery as described herein. For example, topical compositions may be administered orally, anally, rectally, nasally, or in the ear or vagina. Topical compositions may also be administered to the skin surface.

[0099] This disclosure may be implemented in other forms without departing from its spirit or essential features, and therefore, the following claims should be referenced to the scope of the invention rather than the foregoing specification. Furthermore, the diagrams of the configurations described herein are for providing a general understanding of various embodiments and are not intended to be a complete description. Those skilled in the art will see many other configurations by considering the above description. Other configurations may be utilized and derived therefrom, and logical substitutions and modifications may be made without departing from the scope of this disclosure.

[0100] This disclosure is intended to encompass all applications or variations of various embodiments and configurations of the present invention. Combinations of the above configurations, and other configurations not specifically described herein, will become apparent to those skilled in the art by considering the above description. Accordingly, this disclosure is not intended to be limited to any particular preferred configuration disclosed for carrying out the present invention, but rather to encompass all embodiments and configurations included in the appended claims.

[0101] Various elements described herein are described, for example, as substitutes or combinations of substitutes in the list of selectable active ingredients, components, or compositions. It should be understood that embodiments may include one or more, or all, of these elements. Thus, this description includes embodiments that include all of these elements individually and embodiments that include all of these elements in combination. Any composition or component disclosed herein may be expressly excluded in embodiments. In various embodiments, topical compositions may not contain biologics, nucleic acids, corn, soybeans, monosaccharides, disaccharides, milk, collagen, nuts, fish, crustaceans, penicillin, hydrocarbons, alcohols, NSAIDs, anticonvulsants, gluten, or combinations thereof. In one example, a topical composition may not contain sulfonamides, in addition to not containing one or more of the above.

[0102] As used herein, the singular is intended to include "at least one" or "one or more" unless otherwise specified. Therefore, in this specification, it is used to refer to one or more of the objects (i.e., "at least one"). For example, "component" means one or more components, and therefore multiple components may be assumed and may be used in application of the embodiments described. Furthermore, unless otherwise specified in the context, the use of a singular noun includes the plural, and the use of a plural noun includes the singular. In addition, the conjunctions "and" and "or" are used herein according to their accepted usage. For example, "x and y" refers to "x" and "y". On the other hand, "x or y" refers to "x", "y", or both "x" and "y", and "either x or y" indicates exclusivity.

[0103] Numerical ranges described herein include all values ​​and ranges from the lower limit to the upper limit. For example, if a range is described as 1 to 50, values ​​such as 2 to 40, 10 to 30, 1 to 3, or 2, 25, 39 are considered to be explicitly listed herein. These are merely examples of what is specifically intended, and any possible combination of numbers and ranges between the listed minimum and maximum values ​​is considered to be explicitly listed herein. Numbers modified with the words "approximately" or "about" are intended to include ±10% of the modified number.

Claims

1. A topical composition for oral absorption in the oral cavity of a subject to treat type 2 diabetes, chronic weight maintenance, or binge eating, wherein the topical composition comprises a GLP-1 receptor agonist suspended in a self-emulsifying anhydrous suspension base, the self-emulsifying anhydrous suspension base comprising glyceryl stearate, glyceryl monostearate, glyceryl distearate, PEG-32 stearate, lecithin containing phosphatidylcholine and lysophosphatidylcholine, caprylic / capric triglyceride, alcohol, oleic acid, ascorbyl palmitate, tocopherol (vitamin E), and apricot kernel oil PEG-6 ester.

2. The topical composition according to claim 1, wherein the topical composition is configured to self-emulsify in place and form liposomes upon contact with an aqueous liquid in the oral cavity.

3. The topical composition according to claim 2, wherein the topical composition is a preliposome composition.

4. The topical composition according to claim 3, wherein the GLP-1 receptor agonist associates between the bilayers of liposomes when the topical composition self-emulsifies.

5. The topical composition according to claim 4, wherein polycarbophil, glyceryl distearate, and glyceryl monostearate form a protective matrix film by self-emulsification, the protective matrix film adheres to the mucous membrane to extend the contact time, and minimizes initial drug contact with taste buds to reduce bitterness.

6. The topical composition according to claim 1, wherein the topical composition is configured to self-emulsify and form a micelle system.

7. The topical composition according to claim 6, wherein the GLP-1 receptor agonist associates with micelles of a micelle system.

8. The topical composition according to claim 7, wherein a micelle encapsulates a GLP-1 receptor agonist in its core.

9. The topical composition according to claim 8, wherein the micelle system includes a mixed micelle system.

10. The topical composition according to claim 9, wherein polycarbophil, glyceryl distearate, and glyceryl monostearate form a protective matrix film by self-emulsification, the protective matrix film adheres to the mucous membrane to extend the contact time, and minimizes initial drug contact with taste buds to reduce bitterness.

11. The topical composition according to claim 10, comprising a self-emulsifying pre-liposome micelle hybrid drug delivery system that self-emulsifies in situ to form a micelle and liposome drug delivery system.

12. The topical composition according to claim 1, comprising a self-emulsifying microemulsion hybrid drug delivery system.

13. The topical composition according to claim 12, wherein polycarbophil, glyceryl distearate, and glyceryl monostearate form a protective matrix film by self-emulsification, the protective matrix film adheres to the mucous membrane to extend the contact time, and the initial drug contact with taste buds is minimized to reduce bitterness.

14. A topical composition according to any one of compositions 1 to 13, comprising a humectant, a fragrance, a sweetener, or a mixture of these.

15. The topical composition according to claim 14, wherein the wetting agent comprises propylene glycol, glycerin, or both.

16. The topical composition according to claim 14, wherein the fragrance comprises marshmallow oil fragrance.

17. The topical composition according to claim 14, wherein the sweetener comprises sucralose, silaitia grosvenorii monk fruit, or both.

18. The topical composition according to any one of claims 1 to 13, further comprising magnesium stearate, microcrystalline cellulose, povidone, and sodium salcaprozate.

19. A topical composition according to any one of claims 1 to 13, wherein oral absorption is sublingual absorption.

20. A topical composition according to any one of claims 1 to 13, wherein oral absorption is by buccal mucosal absorption.

21. The topical composition according to any one of claims 1 to 13, wherein the topical composition is configured to be administered sublingually or into the buccal mucosa by a syringe or dropper.

22. The topical composition according to any one of claims 1 to 13, wherein the topical composition is in the form of a solution, a semi-solid, or a solid.

23. The topical composition according to any one of claims 1 to 13, comprising a dosage form selected from a solution, suspension, gel, paste, tablet, or lozenge.

24. The topical composition according to any one of claims 1 to 13, wherein the GLP-1 receptor agonist is semaglutide.

25. The topical composition according to claim 24, wherein semaglutide is solubilized.

26. A topical composition for oral absorption in the oral cavity of a subject to treat type 2 diabetes, chronic weight maintenance, or binge eating, wherein the topical composition comprises a GLP-1 receptor agonist suspended in a self-emulsifying anhydrous suspension base.

27. The topical composition according to claim 26, wherein the self-emulsifying anhydrous suspension base comprises stearic acid, lecithin, triglycerides, and polycarbophil.

28. The topical composition according to claim 27, wherein the stearic acid comprises glyceryl stearate, glyceryl monostearate, and glyceryl distearate.

29. The topical composition according to claim 28, wherein the stearic acid further comprises PEG-32 stearate.

30. The topical composition according to any one of claims 27 to 29, comprising lecithin, phosphatidylcholine, and lysophosphatidylcholine.

31. A topical composition according to any one of claims 27 to 30, wherein the triglyceride comprises caprylic / capric acid triglyceride.

32. The topical composition according to any one of claims 27 to 31, wherein the self-emulsifying anhydrous suspension base further comprises an alcohol, oleic acid, ascorbyl palmitate, and tocopherol (vitamin E).

33. The topical composition according to claim 32, wherein the self-emulsifying anhydrous suspension base further comprises apricot kernel oil PEG-6 ester.

34. The topical composition according to claim 26, wherein the self-emulsifying anhydrous suspension base comprises glyceryl stearate, glyceryl monostearate, glyceryl distearate, PEG-32 stearate, lecithin containing phosphatidylcholine and lysophosphatidylcholine, caprylic / capric triglyceride, alcohol, oleic acid, ascorbyl palmitate, tocopherol (vitamin E), and apricot kernel oil PEG-6 ester.

35. The topical composition according to any one of claims 26 to 34, wherein the topical composition is configured to self-emulsify in place and form liposomes upon contact with an aqueous liquid in the oral cavity.

36. The topical composition according to claim 35, wherein the topical composition is a preliposome composition.

37. The topical composition according to claim 36, wherein the GLP-1 receptor agonist associates between the bilayers of liposomes when the topical composition self-emulsifies.

38. The topical composition according to claim 37, wherein polycarbophil, glyceryl distearate, and glyceryl monostearate form a protective matrix film by self-emulsification, the protective matrix film adheres to the mucous membrane to extend the contact time, and the initial drug contact with taste buds is minimized to reduce bitterness.

39. The topical composition according to claim 26, wherein the topical composition is configured to self-emulsify and form a micelle system.

40. The topical composition according to claim 39, wherein the GLP-1 receptor agonist associates with micelles of a micelle system.

41. The topical composition according to claim 40, wherein a micelle encapsulates a GLP-1 receptor agonist in its core.

42. The topical composition according to claim 41, wherein the micelle system includes a mixed micelle system.

43. The topical composition according to claim 42, wherein polycarbophil, glyceryl distearate, and glyceryl monostearate form a protective matrix film by self-emulsification, the protective matrix film adheres to the mucous membrane to extend the contact time, and the initial drug contact with taste buds is minimized to reduce bitterness.

44. The topical composition according to any one of claims 26 to 43, comprising a self-emulsifying pre-liposome micelle hybrid drug delivery system that self-emulsifies in situ to form a micelle and liposome drug delivery system.

45. The topical composition according to any one of claims 26 to 44, comprising a self-emulsifying microemulsion hybrid drug delivery system.

46. The topical composition according to claim 45, wherein polycarbophil, glyceryl distearate, and glyceryl monostearate form a protective matrix film by self-emulsification, the protective matrix film adheres to the mucous membrane to extend the contact time, and the initial drug contact with taste buds is minimized to reduce bitterness.

47. A topical composition according to any one of claims 26 to 46, comprising a humectant, a fragrance, a sweetener, or a mixture of these.

48. The topical composition according to claim 47, wherein the wetting agent comprises propylene glycol, glycerin, or both.

49. The topical composition according to claim 47 or 48, wherein the fragrance comprises marshmallow oil fragrance.

50. A topical composition according to any one of claims 47 to 49, wherein the sweetener comprises sucralose, silaitia grosvenorii monk fruit, or both.

51. The topical composition according to any one of claims 26 to 50, further comprising magnesium stearate, microcrystalline cellulose, povidone, and sodium salcaprozate.

52. A topical composition according to any one of claims 26 to 51, wherein oral absorption is sublingual absorption.

53. A topical composition according to any one of claims 26 to 52, wherein oral absorption is absorption through the buccal mucosa.

54. The topical composition according to any one of claims 26 to 53, wherein the topical composition is configured to be administered sublingually or into the buccal mucosa by a syringe or dropper.

55. The topical composition according to any one of claims 26 to 54, wherein the topical composition is in the form of a solution, a semi-solid, or a solid.

56. The topical composition according to any one of claims 26 to 55, comprising a dosage form selected from a solution, suspension, gel, paste, tablet, or lozenge.

57. The topical composition according to any one of claims 26 to 56, wherein the GLP-1 receptor agonist is semaglutide.

58. The topical composition according to claim 57, wherein semaglutide is solubilized.

59. A topical composition according to any one of claims 26 to 58, wherein the anhydrous suspension base comprises a synergistic combination of about 0.5 w / w% to about 10 w / w% phosphatidylcholine and about 0.1 w / w% to about 1 w / w% lysophosphatidylcholine.

60. A topical composition according to any one of claims 26 to 59, wherein the anhydrous suspension base comprises about 3 w / w% phosphatidylcholine and about 0.36 w / w% lysophosphatidylcholine.

61. The topical composition according to any one of claims 26 to 60, wherein the concentration of the GLP-1 receptor agonist is about 0.001% to about 10% (w / v).

62. The topical composition according to any one of claims 26 to 60, wherein the concentration of the GLP-1 receptor agonist is 0.001% to about 0.1% (w / v).

63. The topical composition according to any one of claims 26 to 60, wherein the concentration of the GLP-1 receptor agonist is about 0.05% to about 1% (w / v).

64. The topical composition according to any one of claims 26 to 60, wherein the concentration of the GLP-1 receptor agonist is about 0.05% to about 0.5% (w / v).

65. The topical composition according to any one of claims 26 to 60, wherein the concentration of the GLP-1 receptor agonist is about 0.08% to about 0.15% (w / v).

66. The topical composition according to any one of claims 26 to 60, wherein the concentration of the GLP-1 receptor agonist is about 2% to about 5% (w / v).

67. The topical composition according to any one of claims 26 to 60, wherein the concentration of the GLP-1 receptor agonist is less than 0.5% (w / v).

68. The topical composition according to any one of claims 26 to 60, wherein the concentration of the GLP-1 receptor agonist is less than 1.5% (w / v).

69. A topical composition to be orally absorbed in the oral cavity of a subject for the treatment of type 2 diabetes, chronic weight maintenance, or overeating, wherein the topical composition to be orally absorbed comprises semaglutide suspended in an anhydrous suspension base, and further comprises phosphatidylcholine, lysophosphatidylcholine, polycarbophil, glyceryl distearate, glyceryl monostearate, magnesium stearate, microcrystalline cellulose, povidone, and sodium salcaprosate.

70. The topical composition according to claim 69, which is orally absorbed topical composition, further comprising caprylic acid / capric acid triglyceride.

71. The topical composition according to claim 70, further comprising sucralose, monk fruit extract, and marshmallow oil fragrance.

72. A method for treating type 2 diabetes, comprising preparing a topical composition according to any one of claims 1 to 71.

73. A method for treating chronic weight maintenance, comprising preparing a topical composition according to any one of claims 1 to 71.

74. A method for treating an overeating condition, comprising preparing a topical composition according to any one of claims 1 to 71.

75. A method for treating type 2 diabetes, comprising administering the topical composition according to any one of claims 1 to 71 into the oral cavity of a subject who requires it.

76. A method for treating chronic weight maintenance, comprising administering the topical composition according to any one of claims 1 to 71 into the oral cavity of a subject who requires it.

77. A method for treating an overeating condition, comprising administering the topical composition according to any one of claims 1 to 71 into the oral cavity of a subject who requires it.

78. The method according to any one of claims 75 to 77, wherein the topical composition is administered in a dose of about 1 mg to about 30 mg.

79. The method according to any one of claims 75 to 77, wherein the topical composition is administered transmucosally in a dose of about 0.1 mg to about 1 mg.

80. The method according to any one of claims 75 to 79, wherein the topical composition is administered to the skin of a subject requiring transdermal or transmucosal delivery, or to the mucous membrane of the vagina, rectum, oral cavity, or nasal cavity.

81. A method for treating type 2 diabetes, chronic weight maintenance, or a state of overeating, the method comprising administering a topical composition into the oral cavity of a subject and allowing it to be absorbed orally therein, wherein the topical composition comprises a pharmaceutically effective amount of semaglutide suspended in an anhydrous suspension base, and the topical composition comprises phosphatidylcholine, lysophosphatidylcholine, polycarbophil, glyceryl distearate, and glyceryl monostearate.

82. The method according to claim 81, wherein the topical composition further comprises sucralose, silaitia grosvenori (monk fruit), or both.

83. The method according to claim 82, wherein the topical composition further comprises a marshmallow oil fragrance.

84. The method according to claim 81, wherein the topical composition further comprises magnesium stearate, microcrystalline cellulose, povidone, and sodium salcaprozate.

85. The method according to claim 84, wherein the topical composition further comprises caprylic acid / capric acid triglyceride.

86. The method according to claim 85, wherein the topical composition further comprises sucralose, monk fruit extract, and marshmallow oil fragrance.

87. A method for preparing a topical composition for topical administration into the oral cavity for oral absorption to treat type 2 diabetes, chronic weight maintenance, or a state of overeating, the method comprising mixing semaglutide powder with an anhydrous suspension base to form a suspension, the suspension being prepared to form self-emulsifying liposomes in the aqueous environment of the oral cavity.

88. The method according to claim 87, wherein the suspension comprises phosphatidylcholine and lysophosphatidylcholine.

89. The method according to claim 88, wherein the suspension further comprises polycarbophil.

90. The method according to claim 89, wherein the suspension further comprises glyceryl distearate and glyceryl monostearate.

91. The method according to claim 90, wherein the suspension further comprises caprylic acid / capric acid triglyceride.

92. The method according to claim 90, wherein the suspension further comprises sucralose, silaitia grosvenori (monk fruit), or both.

93. The method according to claim 92, wherein the suspension further comprises marshmallow oil fragrance.

94. The method according to claim 87, wherein the suspension further comprises magnesium stearate, microcrystalline cellulose, povidone, and sodium salcaprozate.

95. The method according to claim 94, wherein the suspension further comprises polycarbophil.

96. The method according to claim 95, wherein the suspension further comprises glyceryl distearate and glyceryl monostearate.

97. The method according to claim 96, wherein the suspension further comprises phosphatidylcholine and lysophosphatidylcholine.

98. The method according to claim 97, wherein the suspension further comprises caprylic acid / capric acid triglyceride.

99. The method according to claim 98, wherein the suspension further comprises sucralose, silaitia grosvenori (monk fruit), or both.

100. The method according to any one of claims 87 to 99, wherein the semaglutide associates with liposomes suspended in a carrier.

101. A method for treating type 2 diabetes, chronic weight maintenance, or a state of overeating, the method comprising administering a topical composition into the oral cavity of a subject and allowing it to be absorbed orally therein, wherein the topical composition comprises a pharmaceutically effective amount of semaglutide suspended in an anhydrous suspension base, and the topical composition comprises phosphatidylcholine, lysophosphatidylcholine, polycarbophil, glyceryl distearate, and glyceryl monostearate.

102. The method according to claim 101, wherein the topical composition further comprises sucralose, silaitia grosvenori (monk fruit), or both.

103. The method according to claim 102, wherein the topical composition further comprises a marshmallow oil fragrance.

104. The method according to claim 101, wherein the topical composition further comprises magnesium stearate, microcrystalline cellulose, povidone, and sodium salcaprozate.

105. The method according to claim 104, wherein the topical composition further comprises caprylic acid / capric acid triglyceride.

106. The method according to claim 105, wherein the topical composition further comprises sucralose, silaitia grosvenori (monk fruit) fruit, and marshmallow oil fragrance.

107. The method according to claim 101, wherein oral absorption is sublingual absorption.

108. The method according to claim 101, wherein oral absorption is absorption through the buccal mucosa.

109. The method according to claim 101, wherein the topical composition self-emulsifies in the aqueous environment of the oral cavity to form a mixed micelle system.

110. The method according to claim 109, wherein the topical composition further comprises sucralose, silaitia grosvenori (monk fruit), or both.

111. The method according to claim 110, wherein the topical composition further comprises a marshmallow oil fragrance.

112. The method according to claim 109, wherein the topical composition further comprises magnesium stearate, microcrystalline cellulose, povidone, and sodium salcaprozate.

113. The method according to claim 112, wherein the topical composition further comprises caprylic acid / capric acid triglyceride.

114. The method according to claim 113, wherein the topical composition further comprises sucralose, monk fruit (Siraitia grosvenori), and marshmallow oil fragrance.

115. The method according to claim 109, wherein oral absorption is absorption through the buccal mucosa.

116. The method according to claim 109, wherein oral absorption is sublingual absorption.

117. The method according to claim 115, wherein the topical composition further comprises magnesium stearate, microcrystalline cellulose, povidone, and sodium salcaprozate.

118. The method according to claim 101, wherein the local composition comprises a mixed micelle system.

119. The method according to claim 101, wherein the topical composition comprises mixed micelles and liposomes.

120. The method according to claim 101, wherein the topical composition comprises liposomes associated with semaglutide.

121. The method according to claim 101, wherein the topical composition self-emulsifies in the aqueous environment of the oral cavity to form liposomes associated with semaglutide.

122. The method according to claim 101, wherein the topical composition self-emulsifies in the aqueous environment of the oral cavity to form a mixed micelle system, or liposomes associated with a mixed micelle system and semaglutide, and the topical composition is administered orally in liquid dosage form.

123. A method for treating type 2 diabetes, chronic weight maintenance, or a state of overeating, the method comprising administering a pharmaceutically effective amount of a topical composition comprising semaglutide and a base to the skin of a subject or to the mucous membrane of the vagina, rectum, oral cavity, or nasal cavity for transdermal or transmucosal delivery.

124. The method according to claim 123, wherein the base comprises a cream, ointment, solution, lotion, suspension, gel, paste, or foam.

125. The method according to claim 124, wherein semaglutide is encapsulated within liposomes suspended in a base.

126. The method according to claim 125, wherein semaglutide is associated with liposomes suspended in a base.

127. The method according to claim 123, wherein semaglutide is encapsulated within liposomes suspended in a base.

128. The method according to claim 127, wherein the base is an anhydrous suspension base.

129. The method according to claim 123, further comprising a fragrance as a topical composition.

130. A method for treating type 2 diabetes, chronic weight maintenance, or a state of overeating, the method comprising administering a pharmaceutically effective amount of a topical composition comprising semaglutide suspended in an anhydrous suspension base into the oral cavity of a subject and allowing it to be absorbed orally therein.

131. The method according to claim 130, wherein the semaglutide is obtained from or derived from a commercially available oral tablet containing crushed semaglutide.

132. A method for preparing a topical composition for oral absorption by local administration into the oral cavity, the method comprising preparing a suspension by compounding the powder of a commercially available GLP-1 receptor agonist oral tablet, which has been crushed, with a base.

133. The method according to claim 132, wherein the GLP-1 receptor agonist is semaglutide.

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