Development of an in vitro dissolution model to predict the in vivo behavior of poorly soluble compounds

One of the challenges of biopharmaceutics research is correlating in vitro drug release information with the in vivo drug profiles often known as in vitro-in vivo correlations (IVIVC). These have huge cost savings in pharmaceutical industry. This dissertation describes the development of a novel in vitro dissolution model that has been designed to evaluate the in vitro release of poorly water-soluble model compounds so as to predict their in vivo behavior. The flow through apparatus (USP 4) has been coupled with the compendial dissolution apparatus (USP 2). A bi-phasic dissolution medium has been used to achieve sink conditions. The dissolved drug from the aqueous phase is continuously extracted into the organic phase of the biphasic dissolution medium, mimicking the dynamic process of in vivo absorption. The model can successfully discriminate between the bioequivalent and non-bioequivalent formulations and can be used to establish IVIVC. It was concluded that the model will serve as a surrogate for bioequivalence studies and to support biowaivers.