Formulations for enhanced bioavailability of orally administered polar agents

摘要

A composition is described having improved oral permeability of polar agents such as neuraminidase inhibitors. The composition includes one or more polar agents and one or more permeability enhancers such that the composition increases the amount of the polar agent capable of being transported across a Caco-2 cell membrane by at least 150% relative to the amount capable of being transported across the Caco-2 Cell membrane in the absence of the permeability enhancer. Oral dosage forms including the composition, and methods of treating or preventing influenza infection are also provided.

主权项

1. An oral dosage form for release of a polar agent therefrom in the duodenum, said oral dosage form comprising a composition having an enteric- or pH-sensitive coating or layer surrounding same, said composition comprising:
a therapeutically effective amount of a polar agent having at least one group that confers a degree of partial or permanent charge on the polar agent that is greater than or equal to the charge of an hydroxyl group, a carboxyl group, an imidazole group, an amino group, a guanidino group, a phosphate group, or a sulfate group, and a permeability-enhancing amount of a permeability enhancer comprising glycerol, wherein the permeability enhancer is present in the composition at a concentration from 5% to 95% of the combined weight of the polar agent and the permeability enhancer; and wherein the permeability enhancer promotes paracellular or transcellular transport such that the amount of the polar agent transported across a Caco-2 cell membrane by said oral dosage form is increased by at least 150% relative to the amount transported across the Caco-2 Cell membrane in the absence of the permeability enhancer.