NOVEL FORMULATION STRATEGIES FOR IMPROVING ORAL BIOAVAILABILITY OF DRUGS WITH POOR MEMBRANE PERMEATION OR PRESYSTEMIC METABOLISM

The oral route is most preferred for chronic drug therapy. Poor oral b ioavailability has the consequences of more variable and poorly contro lled plasma concentrations and drug effects, in addition to possibly i ncreased product cost. In this review, the most common causes of low o ral bioavailability are categorized, and formulation strategies to imp rove bioavailability are summarized. Various methods that can be used to help identify the cause of low bioavailability are discussed. The f ocus of this article is on poor membrane permeation and presystemic de gradation problems; solubility/dissolution rate problems are discussed only briefly. Poor membrane permeation and presystemic degradation pr oblems are typically encountered in the efforts to develop oral protei ns, peptides, and peptide mimics. Formulation strategies reviewed incl ude the use of metabolism inhibitors, membrane permeation enhancers, i on pairing and complexation, and particulate carriers. Also reviewed a re lipid and surfactant formulations, which have been shown to increas e bioavailability by various mechanisms and which are only beginning t o be understood and optimized.