Oral enhanced pharmaceutical composition comprising semaglutide

Abstract

The present invention relates to an oral pharmaceutical composition comprises semaglutide, SNAC (Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate), sodium caprate and one or more pharmaceutically acceptable excipients.

Description

[0001]DESCRIPTION ORAL ENHANCED PHARMACEUTICAL COMPOSITION COMPRISING SEMAGLUTIDE Field of Invention The present invention relates to an oral pharmaceutical composition comprises 5 semaglutide, SNAC (Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate), sodium caprate and one or more pharmaceutically acceptable excipients. Background of the Invention The development of oral formulations for peptide-based drugs has long presented 10 significant challenges due to the inherent instability of peptides in the gastrointestinal (GI) tract and their poor permeability across the intestinal epithelium. Various strategies have been employed to overcome these barriers, including the use of enzyme inhibitors, absorption enhancers, and advanced delivery systems. 15 Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been primarily administered via subcutaneous injection due to its susceptibility to degradation by proteolytic enzymes and its limited permeability through the intestinal mucosa. The advancement of oral formulations for such peptides aims to improve patient compliance and broaden the therapeutic use of these compounds. 20 One of the key approaches in the development of an oral semaglutide formulation has been the incorporation of absorption enhancers. Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) has been identified as an effective enhancer for improving the bioavailability of semaglutide. SNAC facilitates the transcellular absorption of 25 semaglutide by transiently increasing the permeability of the epithelial cell membrane, thus allowing the peptide to enter the bloodstream more efficiently. In view of the foregoing, there is a need to improve stability and high patient compliance in oral compositions comprising semaglutide, SNAC, sodium caprate and one or more 30 pharmaceutically acceptable excipient. The present invention provides a solution to these problems by providing novel compositions comprising semaglutide, SNAC, sodium caprate and one or more pharmaceutically acceptable excipient. The combination of sodium caprate and SNAC with Semaglutide represents a significant advancement in oral peptide drug delivery, providing a viable alternative to injectable formulations. This approach not only enhances the bioavailability of semaglutide but also aligns with ongoing efforts to develop patient-friendly oral peptide therapies. These solutions will be described in detail. 5 Summary of the Invention The present invention provides an oral pharmaceutical composition, preferably tablet comprising semaglutide, SNAC, sodium caprate and one or more pharmaceutically acceptable excipients. 10 The oral pharmaceutical composition in present invention comprises SNAC in an amount of between 30.00 – 50.00% (w / w). The oral pharmaceutical composition in present invention comprises SNAC in an amount 15 of between 40.00 – 45.00% (w / w). The oral pharmaceutical composition in present invention comprises sodium caprate in an amount of between 25.00 – 40.00% (w / w). 20 The oral pharmaceutical composition in present invention comprises sodium caprate in an amount of between 30.00 – 35.00% (w / w). In other aspect of the present invention a process for preparing tablet compositions comprising the steps of 25 a. Dissolving binder in solvent, b. Dissolving two absorption enhancers in the mixture of binder and solvent, c. Spraying mixture of step “b” upon Semaglutide particles using fluid bed drier, d. Drying and mixing semaglutide granules with diluent, e. Lubricating with lubricant, 30 f. Compressing into tablets. Detailed Description of the Invention The present invention relates to preparation of pharmaceutical compositions comprising semaglutide in the treatment of type 2 diabetes. The present invention relates to preparation of pharmaceutical compositions comprising semaglutide, and one or more pharmaceutically acceptable carriers or excipients. 5 The present invention relates to preparation of pharmaceutical compositions comprising semaglutide and one or more pharmaceutically acceptable carriers or excipients, comprising at least one absorption enhancer. The present invention relates to preparation of pharmaceutical compositions comprising 10 semaglutide and one or more pharmaceutically acceptable carriers or excipients, comprising SNAC as a absorption enhancer. The present invention relates to preparation of pharmaceutical compositions comprising semaglutide and one or more pharmaceutically acceptable carriers or excipients, 15 comprising sodium caprate as a absorption enhancer. The present invention relates to preparation of pharmaceutical compositions comprising semaglutide and one or more pharmaceutically acceptable carriers or excipients, comprising SNAC and sodium caprate as a absorption enhancers. 20 The oral pharmaceutical composition in present invention comprises SNAC in an amount of between 30.00 – 50.00% (w / w). The oral pharmaceutical composition in present invention comprises SNAC in an amount 25 of between 40.00 – 45.00% (w / w). The oral pharmaceutical composition in present invention comprises sodium caprate in an amount of between 25.00 – 40.00% (w / w). 30 The oral pharmaceutical composition in present invention comprises sodium caprate in an amount of between 30.00 – 35.00% (w / w). The aspects and disclosures according to the present invention, in particular an oral pharmaceutical composition comprising semaglutide, SNAC, sodium caprate and one or 35 more pharmaceutically acceptable excipients, defined hereinbefore and hereinafter. Excipients used in a formulation may adversely affect physicochemical and pharmacokinetic properties. These excipients can interact with the active ingredient. For this reason, while developing the formulation, the substances to be used in addition to the active substance must be carefully and consciously selected. 5 Preferably, the present invention relates to an oral pharmaceutical composition comprising semaglutide, SNAC, sodium caprate and one or more pharmaceutically acceptable excipients, wherein the excipients are selected from the group including, but are not limited to diluents, lubricants, glidants, binders, disintegrants, antioxidants, 10 solubility increasing agents, preservatives, buffering agents, solvents, flavoring agent, stabilizers, sweetening agent, mixtures thereof. and other materials known to one of ordinary skill in the art and the mixtures thereof. Diluents are essential components in tablet compositions, serving to increase the volume 15 of the formulation, ensuring uniform distribution of the active pharmaceutical ingredient (API), and enhancing the stability and manufacturability of the product. They help achieve consistent dosing, improve the flow properties of powders, and ensure that tablets and capsules reach a practical size for handling and administration. Diluents also contribute to the appearance and taste of the final product, thereby enhancing patient compliance 20 and acceptability. In tablet formulations, they provide the necessary bulk for compression, while in capsules, they fill the dosage unit to the desired weight and volume. For injectable formulations, diluents help maintain isotonicity and stability. Commonly used diluents in tablet compositions include lactose, which is valued for its 25 compressibility and compatibility with most APIs; microcrystalline cellulose (MCC), known for its excellent binding properties; and dicalcium phosphate (DCP), which offers good flowability. Starch is used for its binding and disintegration properties, while mannitol and sorbitol are favored for their pleasant mouthfeel and sweet taste, respectively. Calcium carbonate is commonly used in antacid formulations, sodium 30 chloride is used in small amounts in injectable formulations, and sucrose is used in chewable tablets and lozenges for its sweetness. Microcrystalline cellulose (MCC) is highly regarded for its exceptional binding properties and ability to enhance the hardness and stability of tablets. It also improves the flow properties of powder blends, making it a versatile diluent in various solid dosage forms. In preferred embodiment in the present invention amount of diluent can be between 15.00-60.00% (w / w). In preferred embodiment in present invention diluent can be microcrystalline cellulose. 5 In preferred embodiment in the present invention amount of microcrystalline cellulose can be between 15.00-25.00% (w / w). Lubricants are crucial excipients in tablet compositions, primarily used to reduce friction during the tablet manufacturing process. They help prevent the tablet blend from sticking 10 to the equipment, ensuring a smooth and efficient production process. Lubricants improve the flow of the tablet mixture through the machinery, enhancing the uniformity and consistency of the final product. Additionally, they aid in the ejection of tablets from the die cavity, preventing damage and ensuring the integrity of the tablets. 15 Commonly used lubricants in tablet compositions include magnesium stearate, stearic acid, talc, sodium stearyl fumarate, colloidal silicon dioxide, and polyethylene glycol (PEG). In preferred embodiment in the present invention amount of diluent can be between 0.5-3.0% (w / w). 20 In preferred embodiment in present invention lubricant can be magnesium stearate. In preferred embodiment present invention amount of lubricant can be between 0.5-3.0% (w / w). More preferably, amount of magnesium stearate can be between 0.5-2.0% (w / w), even more preferably amount of magnesium stearate can be 1.75% (w / w). 25 Commonly used binders in pharmaceutical compositions include polyvinylpyrrolidone (PVP), hydroxypropyl methylcellulose (HPMC) and starch. Acacia and gelatin are natural binders that provide strong adhesion, while pregelatinized starch is favored for its immediate binding capabilities. Corn syrup solids are used for their sweetness and binding properties in chewable tablets, and ethyl cellulose is commonly used in 30 controlled-release formulations. In a preferred embodiment of the present invention, the amount of binder can be between 0.50-2.00% (w / w). In a preferred embodiment of the present invention, the binder can be povidone. In a preferred embodiment of the present invention, the amount of povidone can be between 0.50-2.00% (w / w), even more preferably amount of povidone can be 1.00%. 5 In the present invention, SNAC and sodium caprate are used as absorption enhancers. Absorption enhancers are agents used in pharmaceutical formulations to improve the absorption of drugs, especially those that are poorly absorbed through the gastrointestinal (GI) tract. They work by various mechanisms to increase the permeability of the epithelial cells lining the GI tract, thereby facilitating the drug's entry into the 10 systemic circulation. The inventors surprisingly have found that the combination of SNAC and sodium caprate with semaglutide represents a significant advancement in drug delivery, providing a viable alternative to injectable formulations, enhances the bioavailability of semaglutide 15 and develops patient-friendly oral peptide therapies. In present invention water or ethanol can be used as solvent. More preferably water can be selected as a solvent. 20 Preferably the pharmaceutical composition according to the present invention may be in the form of a tablet, capsule, caplet, film-coated tablet, enteric tablet, controlled-release tablet and any similar solid oral dosage forms. The preferred dosage form according to the present invention is tablet form. Commonly available coating materials may be used for coating of tablets. 25 The tablet composition of the present invention comprises below: ^ 0.25% - 5.00% by weight semaglutide, ^ 30.00%-45.00% by weight first absorption enhancer, ^ 25.00%-40.00% by weight second absorption enhancer, 30 ^ 0.50-2.00% by weight binder, ^ 15.00%-25.00% by weight filler, and ^ 0.50%-3.00% by weight lubricant, and ^ Solvent. In other aspect of the present invention a process for preparing tablet composition can be comprises below steps a. Dissolving binder in solvent, b. Dissolving two absorption enhancers in the mixture of binder and solvent, 5 c. Spraying mixture of step “b” upon Semaglutide particles using fluid bed drier, d. Drying and mixing semaglutide granules with diluent, e. Lubricating with lubricant, f. Compressing into tablets. 10 The tablet composition of the present invention comprises below: ^ 0.25% - 5.00% by weight semaglutide, ^ 30.00%-45.00% by weight SNAC, ^ 25.00%-40.00% by weight sodium caprate, ^ 0.50-2.00% by weight povidone, 15 ^ 15.00%-25.00% by weight microcrystalline cellulose, and ^ 0.50%-3.00% by weight magnesium stearate, and ^ Puried water. In other aspect of the present invention a process for preparing tablet composition can be comprises below steps 20 a. Dissolving Povidone in purified water, b. Dissolving SNAC & sodium caprate in the mixture of Povidone and purified water, c. Spraying mixture of step “b” upon Semaglutide particles using fluid bed drier, d. Drying and mixing semaglutide granules with microcrystalline cellulose, 25 e. Lubricating with magnesium stearate, f. Compressing into tablets. In other aspect of a pharmaceutical composition of the present invention for use adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. 30 The term “(w / w)” as used herein, refers to a percentage by weight compared to the total weight of the composition considered. A pharmaceutical composition according to the invention is considered "stable", if during a certain period of time 70%, preferably 80% and most preferably 95% of the initial content of semaglutide, is maintained over said period of time. Experiments 5 Stability Results The stability of the product was monitored under the following three conditions. During the stability period, the product was found to meet the specifications. 25°C ± 2°C / %60 RH ± %5 RH 10 30°C ± 2°C / %65 RH ± %5 RH 40°C ± 2°C / %75 RH ± %5 RH Result of the stability study indicates that present semaglutide composition in accordance with the present invention exhibits excellent storage stability. 15 During the stability period, the product was found to comply with specifications. Examples Example 1 In another preferred embodiment, the pharmaceutical composition according to 20 invention: Table 1: Pharmaceutical composition comprising semaglutide and relevant excipients Ingredients Amount (w / w %) Semaglutide 0.25%-5.00% One or more absorption enhancer 30.00%-50.00% One or more absorption enhancer 25.00%-40.00% One or more binders 0.50%-2.00% One or more fillers 15.00%-25.00% One or more lubricants 0.50%-3.00% Total 100.00% A process of preparing tablet composition of Example 1: a. Dissolving binder in solvent, b. Dissolving two absorption enhancers in the mixture of binder and solvent, 5 c. Spraying mixture of step “b” upon Semaglutide particles using fluid bed drier, d. Drying and mixing semaglutide granules with diluent, e. Lubricating with lubricant, f. Compressing into tablets. 10 Example 2: In another preferred embodiment, the pharmaceutical composition according to invention: Table 2: Pharmaceutical composition comprising semaglutide and relevant excipients Ingredients Amount (w / w %) Semaglutide 0.25%-5.00% Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC)30.00%-50.00%Sodium Caprate 25.00%-40.00% One or more binders 0.50%-2.00% One or more fillers 15.00%-25.00% One or more lubricants 0.50%-3.00% Total 100.00% 15 A process of preparing tablet composition of Example 2: a. Dissolving binder in solvent, b. Dissolving SNAC & sodium caprate in the mixture of binder and solvent, c. Spraying mixture of step “b” upon Semaglutide particles using fluid bed drier, 20 d. Drying and mixing semaglutide granules with filler, e. Lubricating with lubricant, f. Compressing into tablets.

Claims

CLAIMS 2. An oral pharmaceutical composition comprising semaglutide, characterized in comprising Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate, sodium caprate and one or more pharmaceutically acceptable excipients. 5 3. The oral pharmaceutical composition according to claim 1, wherein amount of Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate is between 30.00-50.00% (w / w).

4. The oral pharmaceutical composition according to claim 1, wherein amount of sodium caprate is between 25.00-40.00% (w / w).

5. The oral pharmaceutical composition according to claim 1 characterized in that composition is in tablet form.

6. A process for preparing tablet composition according to claim 5, comprising the steps of a. Dissolving binder in solvent, b. Dissolving two absorption enhancers in the mixture of binder and solvent, c. Spraying mixture of step “b” upon Semaglutide particles using fluid bed drier, d. Drying and mixing semaglutide granules with diluent, e. Lubricating with lubricant, f. Compressing into tablets.