Formulations for oral administration of active agents
Inventors
Burshtein, Gregory • ROTHNER, Ariel • SCHWARTZ, Phillip M. • GALITZER, Hillel
Assignees
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Publication Number
US-12076373-B2
Publication Date
2024-09-03
Expiration Date
Abstract
A pharmaceutical composition for oral administration is disclosed herein, comprising a therapeutically active agent, SNAC and at least one antacid compound. Further disclosed herein is a pharmaceutical composition unit dosage form for oral administration of a therapeutically active agent is provided herein, the unit dosage form comprising: a core comprising the therapeutically active agent and SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate); and an external layer comprising at least one protective agent selected from the group consisting of an antacid compound and a protease inhibitor. Methods and uses utilizing the aforementioned pharmaceutical compositions, as well as methods and uses utilizing co-administration, by oral administration, of at least one antacid composition, and a composition comprising the therapeutically active agent and SNAC, are further disclosed herein, for use in treating a condition treatable by oral administration of the therapeutically active agent.
Core Innovation
The invention relates to oral delivery of a therapeutically active agent with SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate). It addresses a problem that SNAC is inactivated by stomach acid, including conversion to an insoluble form that reduces SNAC activity and effectiveness for oral peptide/polypeptide delivery. The disclosed compositions are formulated as solid unit dosage forms soluble in gastric fluid and include a therapeutically active agent and SNAC.
To overcome inactivation by stomach acid, the invention provides an external protective strategy using at least one antacid compound and optionally a protease inhibitor. The disclosed compositions include at least one antacid compound in a total amount of at least 0.002 molar equivalent of base, selected from specified antacid compounds. The external protective concept is further implemented in a unit dosage form having a core comprising the therapeutically active agent and SNAC and an external layer comprising at least one protective agent selected from an antacid compound and a protease inhibitor.
In some embodiments, protease inhibitors and antacid protection are combined with SNAC, and the composition may be formulated with an optional protective external layer that avoids an enteric coating. The disclosed performance includes enhanced SNAC dissolution in gastric fluid and increased oral bioavailability, including a reported example where oral co-administration with sodium bicarbonate results in higher absorption of orally administered teriparatide (PTH(1-34)) compared with water.
Claims Coverage
The partial content provides three independent claims. Across these independent claims, the coverage centers on SNAC combined with specified antacid protection and optionally protease inhibitor protection, and on oral formulations that are solid and soluble in gastric fluid, including a unit dosage form that does not comprise an enteric coating.
Solid oral SNAC plus antacid, gastric-fluid soluble unit dosage form
A pharmaceutical composition for oral administration comprising a therapeutically active agent, SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate), and at least one antacid compound in a total amount of at least 0.002 molar equivalent of base, with the pharmaceutical composition formulated as a solid unit dosage form soluble in gastric fluid.
Separate oral co-administration of antacid composition and SNAC therapeutically active agent composition
A method of treating a condition treatable by oral administration of a therapeutically active agent in a subject in need thereof by co-administering by oral administration an antacid composition comprising at least one antacid compound and/or at least one gastric acid secretion inhibitor and a composition comprising the therapeutically active agent and SNAC, wherein the antacid composition and the composition comprising the therapeutically active agent and SNAC do not form a single composition.
Core SNAC therapeutically active agent with non-enteric external protective layer
A pharmaceutical composition unit dosage form for oral administration comprising a core comprising the therapeutically active agent and SNAC and an external layer comprising at least one protective agent selected from an antacid compound in a total amount of at least 0.002 molar equivalent of base and a protease inhibitor, wherein the unit dosage form does not comprise an enteric coating.
Overall, the independent claims define oral SNAC-based therapeutically active agent formulations combined with antacid protection and optionally protease inhibitor protection. Coverage includes both single solid unit dosage forms soluble in gastric fluid and separable co-administration approaches, and it further includes a core/external-layer unit dosage form explicitly excluding an enteric coating.
Stated Advantages
Enhanced SNAC dissolution in gastric fluid.
Increased oral bioavailability.
Increased absorption of orally administered teriparatide (PTH(1-34)) when co-administered with sodium bicarbonate compared with water.
Documented Applications
Oral administration of peptide/polypeptide delivery using SNAC, protected from stomach acid inactivation.
Treatment of a condition treatable by oral administration of a therapeutically active agent in a subject in need thereof.
Oral delivery of teriparatide (PTH(1-34)) with antacid protection.
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