Oral enhanced pharmaceutical compositions

Abstract

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

Description

[0001]DESCRIPTION ORAL ENHANCED PHARMACEUTICAL COMPOSITIONS Field of Invention The present invention relates to an oral pharmaceutical composition comprises 5 semaglutide, SNAC (Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate), at least one alkalizing agent 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, one or more alkalizing agents and 30 one or more pharmaceutically acceptable excipient. The present invention provides a solution to these problems by providing novel compositions comprising semaglutide, SNAC, one or more alkalizing agents and one or more pharmaceutically acceptable excipient. The combination of at least one alkalizing agent 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 5 peptide therapies. These solutions will be described in detail. Summary of the Invention The present invention provides an oral pharmaceutical composition comprising semaglutide, SNAC, at least one alkalizing agent and one or more pharmaceutically 10 acceptable excipients wherein the amount of SNAC is between 30.00 – 50.00 % (w / w). The oral pharmaceutical composition in present invention comprises at least one alkalizing agent in an amount of between 15.00 – 25.00% (w / w). 15 The oral pharmaceutical composition in present invention said composition comprises sodium caprate as an additional absorption enhancer. In other aspect of the present invention a process for preparing tablet compositions, comprising the steps of 20 a. Dissolving binder in solvent, b. Dissolving First absorption enhancer in the mixture of binder and solvent, c. Spraying the mixture of step “b” upon Semaglutide particles using fluid bed drier, d. Drying and mixing semaglutide granules, 25 e. Mixing with at least one alkalizing agent and second absorption enhancer, f. Lubricating with lubricant, g. Compressing into tablets. 30 Detailed Description of the Invention The present invention relates to preparation of pharmaceutical compositions comprising semaglutide, and one or more pharmaceutically acceptable carriers or excipients. The present invention relates to preparation of pharmaceutical compositions comprising semaglutide and one or more pharmaceutically acceptable carriers or excipients, comprising one absorption enhancer. The present invention relates to preparation of pharmaceutical compositions comprising 5 semaglutide and one or more pharmaceutically acceptable carriers or excipients, comprising SNAC as a absorption enhancer. The oral pharmaceutical composition in present invention comprises SNAC in an amount of between 30.00 – 50.00% (w / w). 10 The oral pharmaceutical composition in present invention comprises SNAC in an amount of between 40.00 – 45.00% (w / w). The present invention relates to preparation of pharmaceutical compositions comprising 15 semaglutide and one or more pharmaceutically acceptable carriers or excipients, comprising a absorption enhancer and at least one alkalizing agent. The present invention relates to preparation of pharmaceutical compositions comprising semaglutide and one or more pharmaceutically acceptable carriers or excipients, 20 comprising SNAC and at least one alkalizing agent. The present invention relates to preparation of pharmaceutical compositions comprising semaglutide and one or more pharmaceutically acceptable carriers or excipients, comprising SNAC and calcium hydrogen carbonate as alkalizing agent. 25 The present invention relates to preparation of pharmaceutical compositions comprising semaglutide and one or more pharmaceutically acceptable carriers or excipients, comprising SNAC and calcium hydrogen carbonate, magnesium hydroxide as alkalizing agent. 30 The present invention relates to preparation of pharmaceutical compositions comprising semaglutide and one or more pharmaceutically acceptable carriers or excipients, comprising SNAC and calcium hydrogen carbonate, magnesium hydroxide, aluminium hydroxide as alkalizing agent. The oral pharmaceutical composition in present invention comprises at least one 5 alkalizing agent in an amount of between 15.00 – 25.00% (w / w). The aspects and disclosures according to the present invention, in particular an oral pharmaceutical composition comprising semaglutide, SNAC, one or more alkalizing agent and one or more pharmaceutically acceptable excipients, defined hereinbefore and 10 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 15 active substance must be carefully and consciously selected. Preferably, the present invention relates to an oral pharmaceutical composition comprising semaglutide, SNAC, one or more alkalizing agent and one or more pharmaceutically acceptable excipients, wherein the excipients are selected from the 20 group including, but are not limited to diluents, lubricants, glidants, binders, disintegrants, antioxidants, 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. 25 Lubricants are crucial excipients in film coated tablet compositions, primarily used to reduce friction during the tablet manufacturing process. They help prevent the tablet blend from sticking 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 30 tablets from the die cavity, preventing damage and ensuring the integrity of the tablets. Commonly used lubricants in film coated 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 lubricant can be between 0.5-2.0% (w / w). In preferred embodiment in present invention lubricant can be magnesium stearate. In 5 preferred embodiment present invention amount of lubricant can be between 0.5-2.0% (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). Commonly used binders in pharmaceutical compositions include polyvinylpyrrolidone 10 (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 controlled-release formulations. 15 In a preferred embodiment of the present invention, the amount of binder can be between 0.50-5.00% (w / w). In a preferred embodiment of the present invention, the binder can be povidone. In a 20 preferred embodiment of the present invention, the amount of povidone can be between 0.50-5.00% (w / w), even more preferably amount of povidone can be 1.00%. Commonly used alkalizing agent in pharmaceutical compositions comprising sodium dihydrogen phosphate, disodium dihydrogen phosphate, trisodium phosphate, sodium 25 bicarbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, potassium hydrogen phosphate, dipotassium hydrogen phosphate, tripotassium phosphate, calcium hydrogen carbonate, magnesium hydroxide, aluminium hydroxide and other materials known for such property. 30 In a preferred embodiment of the present invention, the amount of alkalizing agent can be between 15.00% to 25.00% (w / w). 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 systemic circulation. 5 The inventors surprisingly have found that the combination of SNAC and at least one alkalizing agent with semaglutide represents a significant advancement in drug delivery, providing a viable alternative to injectable formulations, enhances the bioavailability of semaglutide and develops patient-friendly oral peptide therapies. 10 In present invention water or ethanol can be used as solvent. More preferably water can be selected as a solvent. Preferably the pharmaceutical composition according to the present invention may be in 15 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 film-coated tablet form. Commonly available coating materials may be used for coating of tablets. 20 In one aspect of the present invention comprises below: ^ 0.25% - 5.00% by weight semaglutide, ^ 30.00%-50.00% by weight first absorption enhancer, ^ 25.00%-40.00% by weight second absorption enhancer, ^ 0.50-2.00% by weight binder, 25 ^ 15.00%-25.00% by weight at least one alkalizing agent, and ^ 0.50%-3.00% by weight lubricant, and ^ Solvent. In one aspect of the present invention a process for preparing tablet compositions, 30 comprising the steps of a. Dissolving binder in solvent, b. Dissolving First absorption enhancer in the mixture of binder and solvent, c. Spraying the mixture of step “b” upon Semaglutide particles using fluid bed drier, d. Drying and mixing semaglutide granules, e. Mixing with at least one alkalizing agent and second absorption enhancer, 5 f. Lubricating with lubricant, g. Compressing into tablets. In another aspect of the present invention comprises below: 10 ^ 0.25% - 5.00% by weight semaglutide, ^ 30.00%-50.00% by weight SNAC, ^ 25.00%-40.00% by weight sodium caprate, ^ 0.50-2.00% by weight povidone, ^ 15.00%-25.00% by weight one or more alkalizing agent, and 15 ^ 0.50%-3.00% by weight magnesium stearate, and ^ Purified water. In another aspect of the present invention a process for preparing tablet compositions, comprising the steps of 20 a. Dissolving povidone in purified water, b. Dissolving Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate in the mixture of povidone and purified water, c. Spraying the mixture of step “b” upon Semaglutide particles using fluid bed drier, 25 d. Drying and mixing semaglutide granules, e. Mixing with at least one alkalizing agent and sodium caprate, f. Lubricating with magnesium stearate, g. Compressing into tablets. 30 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. Experiments Stability Results The stability of the product was monitored under the following three conditions. During 5 the stability period, the product was found to meet the specifications. 25°C ± 2°C / %60 RH ± %5 RH 30°C ± 2°C / %65 RH ± %5 RH 40°C ± 2°C / %75 RH ± %5 RH 10 Result of the stability study indicates that present semaglutide composition in accordance with the present invention exhibits excellent storage stability. During the stability period, the product was found to comply with specifications. 15 Examples Example 1 In another preferred embodiment, the pharmaceutical composition according to invention: Table 1: Pharmaceutical composition comprising semaglutide and relevant excipients Ingredients(Awm / wou%nt) Semaglutide 0.25%-5.00% First absorption enhancer 30.00%-50.00% Second absorption enhancer 25.00%-40.00% One or more binders 0.50%-2.00% One or more alkalizing agents 15.00%-25.00% One or more lubricants 0.50%-3.00% Total 100.00% 20 A process of preparing tablet composition of Example 1: a. Dissolving binder in solvent, b. Dissolving First absorption enhancer in the mixture of binder and solvent, c. Spraying the mixture of step “b” upon Semaglutide particles using fluid bed drier, 5 d. Drying and mixing semaglutide granules, e. Mixing with at least one alkalizing agent and second absorption enhancer, f. Lubricating with lubricant, g. 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% Calcium hydrogen carbonate, magnesium hydroxide15.00%-25.00%One or more lubricants 0.50%-3.00% Total 100.00%15A process of preparing tablet composition of Example 2: a. Dissolving binder in purified water, b. Dissolving Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate in the mixture of binder and purified water, 20 c. Spraying the mixture of step “b” upon Semaglutide particles using fluid bed drier, d. Drying and mixing semaglutide granules, e. Mixing with Calcium hydrogen carbonate, magnesium hydroxide and sodium caprate, f. Lubricating with lubricant, 5 g. Compressing into tablets.

Claims

CLAIMS 1. An oral pharmaceutical composition of semaglutide characterized in comprising 30.00–50.00% (w / w) Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate, at least one 5 alkalizing agent and one or more pharmaceutically acceptable excipients.

2. The oral pharmaceutical composition according to claim 1, wherein amount of alkalizing agent is between 15.00-25.00% (w / w).

3. The oral pharmaceutical composition according to claim 1, characterized in further comprising sodium caprate as an absorption enhancer.

4. The oral pharmaceutical composition according to preceding claims, wherein said composition is in tablet form.

5. A process for preparing tablet compositions according to claim 4, comprising the steps of a. Dissolving binder in purified water, b. Dissolving Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate in the mixture of binder and purified water, c. Spraying the mixture of step “b” upon Semaglutide particles using fluid bed drier, d. Drying and mixing semaglutide granules, e. Mixing with at least one alkalizing agent and additional absorption enhancer, f. Lubricating with lubricant, g. Compressing into tablets.