The Introduction of a New Flexible In Vivo Predictive Dissolution Apparatus, GIS-Alpha (GIS-α), to Study Dissolution Profiles of BCS Class IIb Drugs, Dipyridamole and Ketoconazole

Abstract

The physiological pH changes and peristalsis activities in gastrointestinal (GI) tract have big impact on the dissolution of oral drug products, when those oral drug products include APIs with pH-dependent solubility. It is well documented that predicting the bioperformance of those oral drug products can be challenging using compendial methods. To overcome this limitation, in vivo predictive dissolution apparatuses, such as the transfer model, have been developed to predict bioperformance of oral formulation candidates and drug products. In this manuscript we utilize a new transfer-model dissolution apparatus, the gastrointestinal simulator-α (GIS-α), to characterize its behavior in terms of transfer kinetics and pH, assess its reproducibility and adaptability to mimic different transfer conditions, as well as study dissolution of ketoconazole and dipyridamole as model BCS class IIb compounds. Availability of commercially available dissolution transfer systems with similar configuration to compendial dissolution apparatus, may be helpful to simplify and standardize in vivo predictive dissolution methodologies for BCS class IIb compounds in the future.