Peptide pharmaceutical for oral delivery

Inventors

Stern, William • Consalvo, Angelo P.

Assignees

Enteris Biopharma Inc

Abstract

Acid-containing oral pharmaceutical compositions are provided wherein the pharmaceutical active agents are peptide compounds (i.e., those that include a plurality of amino acids and at least one peptide bond in their molecular structures). Certain barrier layers and/or particulate coated acid are used to reduce any adverse interactions that might otherwise occur between the acid of the compositions and other components of the composition. Use of these barrier layers and/or use of particulate coated acid is believed to promote a more simultaneous release of the components of the composition than is achieved by prior art acid-protection techniques, thus enhancing, and making more consistent, the bioavailability of the active peptide compounds.

Core Innovation

The invention relates to a single dosage form for oral delivery of a physiologically active peptide agent. The dosage form comprises the peptide agent, at least one pharmaceutically acceptable acid, an acid resistant protective vehicle effective to transport the dosage form through the stomach while preventing contact between the active peptide agent and stomach proteases, and a water soluble barrier layer that separates the acid from the protective vehicle.

The amount of acid is selected so that, if added to 10 milliliters of 0.1M aqueous sodium bicarbonate solution, it lowers the pH of the solution to no higher than 5.5. This pH-lowering approach supports more simultaneous release of acid and peptide in the intestines, with the resulting decrease in intestinal pH described as reducing protease activity and supporting peptide stability and bioavailability.

The disclosed examples include coated acid materials such as glucose-coated citric acid and coated particulate acid, and enteric-type protective vehicles. The examples indicate faster dissolution for coated versus uncoated citric acid, improved peptide stability with coated acid, and increased peptide Cmax in dog studies with certain subcoat and undercoat configurations.

Claims Coverage

The document provides one independent claim directed to a single layered oral dosage form for a physiologically active peptide, with acid present in a constrained pH-lowering amount, an acid resistant protective vehicle to prevent contact with stomach proteases, and a water soluble barrier layer separating the acid from that protective vehicle. The independent claim includes the additional limitation that the peptide agent and acid are in the same layer, and dependent claims refine acids and layers with quantitative and component constraints.

Overall, claim coverage centers on a single oral dosage form in which peptide and acid are co-located in the same layer, an acid quantity is defined by a bicarbonate pH-lowering criterion (≤5.5), an acid resistant protective vehicle prevents stomach-protease contact, and a water soluble barrier layer separates the acid from the protective vehicle.

Stated Advantages

Documented Applications