Sex-specific modulation of drug bioavailability with pharmaceutical excipients

The biopharmaceutics classification system (BCS) is a framework for classifying drug substances based on their aqueous solubility and permeability across a biological membrane. It is possible for individuals to request a waiver of in vivo bioequivalence (BE) studies for immediate-release solid oral dosage forms. Nowadays, the Food and Drug Administration allows the biowaiver for BCS Class I and Class III drugs. However, the findings in this thesis call attention to the unearthed loopholes in this regulation, given that formerly considered “inert” pharmaceutical excipients have shown unexpected impacts on the absorption of co-formulated drugs. By virtue of our studies, it has been exposed that a number of excipients used to aid tablet manufacturing or formulation development are able to enhance therapeutic efficacy of the drug by the modulation of transporter activity and expression. This, therefore, could characterize the excipient to have two applications; in manufacturing and drug formulation. Furthermore, the thesis outlines the modifications of the overall function of transporters, simply due to the sex of the organism. As a result, the work reported here emphasizes that the selection of excipients during formulation development is integral in preventing differences in therapeutic efficacy and side effect profiles between males and females