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-10583177-B2
Publication Date
2020-03-10
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 provides an oral pharmaceutical composition comprising a therapeutically active agent together with SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate) and at least one antacid compound selected from a specified group. The therapeutically active agent has a molecular weight in the range of 0.5 kDa to 150 kDa, and the total amount of the at least one antacid compound is at least 1 mg.
The invention further addresses gastric degradation and/or inactivation by using protective agents in a formulation having an internal core and an external layer. In the unit dosage form, a core comprises the therapeutically active agent and SNAC, while an external layer comprises at least one protective agent selected from an antacid compound and a protease inhibitor, with the protective agent release occurring before the core components.
The document also discloses optional formulation features for the unit dosage form, including an enteric coating and functional gastric-fluid solubility/dissolution behavior, as well as formulation design in which antacid/protease protection may be provided by external-layer-only coverage and/or region-specific distributions and gradients. The described approach is directed to oral administration of therapeutic active agents in a range of molecular weights and is particularly framed around enhancing absorption of polypeptides/proteins by preventing SNAC inactivation by stomach acid and reducing gastric proteolysis.
Claims Coverage
The document includes three independent claims, each centered on oral SNAC-containing formulations and/or treatment by co-administering SNAC with gastric protection. Across the independent claims, the coverage includes a composition with therapeutically active agent, SNAC, and specified antacid compounds; a method of treating a condition by co-administering an antacid composition and a SNAC-containing therapeutically active-agent composition; and a unit dosage form with a SNAC-containing core and an external protective layer including antacid and/or protease inhibitor.
Oral SNAC and antacid composition for a specified molecular-weight active agent
A pharmaceutical composition for oral administration comprising a therapeutically active agent having a molecular weight in a range of 0.5 kDa to 150 kDa, SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate), and at least one antacid compound selected from a specified group, wherein the at least one antacid compound is in a total amount of at least 1 mg.
Co-administering oral antacid protection with an oral 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, comprising co-administering by oral administration an antacid composition and a composition comprising the therapeutically active agent and SNAC (sodium 8-N-(2-hydroxybenzoyl)aminocaprylate), wherein the therapeutically active agent has a molecular weight in a range of 0.5 kDa to 150 kDa.
Unit dosage form with SNAC core and protective external layer
A pharmaceutical composition unit dosage form for oral administration 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 an antacid compound in an amount of at least 1 mg and a protease inhibitor.
The claim coverage is anchored in three independent directions: an oral composition that combines therapeutically active agents with SNAC and a specified antacid, a treatment method using oral co-administration of an antacid composition with an oral SNAC-containing therapeutic composition, and a unit dosage form having a SNAC core and an external protective layer containing antacid and/or a protease inhibitor.
Stated Advantages
Bioavailability of orally administered therapeutically active agent is at least 10% higher versus a core-only control.
Antacid-enhanced SNAC dissolution.
Increased absorption of orally administered teriparatide/PTH(1-34) by approximately 35% with sodium bicarbonate co-administration.
Documented Applications
Oral administration of therapeutic active agents, particularly polypeptides/proteins, using SNAC with antacid and/or protease inhibitor protection to enhance absorption.
Oral treatment of a condition treatable by oral administration of a therapeutically active agent by co-administering an antacid composition and a SNAC-containing therapeutically active-agent composition.
Use with teriparatide/PTH(1-34) for enhanced absorption when co-administered with sodium bicarbonate.
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