Dissolution of poorly water-soluble drugs in biphasic media using USP 4 and fiber optic system

A novel in-vitro dissolution system based on the principle of flow-through technique has been designed to evaluate the in-vitro release rate of poorly water-soluble compounds. The flow through apparatus (USP 4) has been coupled with the compendial dissolution apparatus (USP apparatus 2). A bi-phasic dissolution medium is used to achieve sink conditions. The dissolved drug is continuously removed from the aqueous phase into the organic phase of the dissolution medium, mimicking the process of absorption in the systemic circulation. The in vitro release profiles obtained from this dissolution model was able to distinguish the formulation changes of several poorly water-soluble drugs from their dosage forms. For AMG 517, the model drug, excellent rank order correlation has been obtained between the in-vitro release and the in-vivo absorption of the drug from several different dosage forms and their formulations. In addition, for several commercial formulations, the model successfully discriminated between the bioequivalent and non-bioequivalent formulations.