The in vivo predictive dissolution for immediate release dosage of donepezil and danazol, BCS class IIc drugs, with the GIS and the USP II with biphasic dissolution apparatus

Authors: Tsume Y, Igawa N, Drelich AJ, Ruan H, Amidon GE, Amidon GL
Publication: J Drug Deliv Sci Technol
Keywords: dissolution method design, formulation optimization, mechanistic absorption modeling, PBPK model
Software: GastroPlus®

Abstract

The formulation developments and the in vivo assessment of Biopharmaceutical Classification System (BCS) class II drugs are challenging due to their low solubility and high permeability in the human gastrointestinal (GI) tract. Since the pH change in the GI environment influences the drug dissolution of BCS class IIa and IIb drugs but not for IIc drugs, the incorporation of the human GI characteristics into the in vitro dissolution system may not be crucial for BCS class IIc drugs to predict their bioperformance. An absorptive compartment in dissolution apparatus would be important to predict bioperformance of BCS class IIc drugs due to their physicochemical characteristics, low solubility and high permeability.

In this study, an absorptive compartment (biphasic system) was introduced to a gastrointestinal simulator (GIS) and USP dissolution apparatus II for the evaluation of in vivo prediction for BCS class IIc drugs. Those in vitro systems with the biphasic phase were evaluated for the prediction of in vivo dissolution of BCS class IIc drugs, donepezil and danazol, and subsequent absorption. For the evaluation of in vivo dissolution of BCS class IIc drugs, simpler dissolution apparatus, USP II, with the absorptive phase might be adequate a dissolution method to predict in vivo.