Development of an Improved Dissolution Testing Method as an Alternative to Animal Testing

Abstract

This study aimed to evaluate the potential of an improved flow-through cell dissolution method as an alternative to animal testing for predicting the in vivo behavior of immediate-release formulations. Donepezil hydrochloride was selected as the model drug, and both test and reference formulations were used. Comparative dissolution studies were conducted under various conditions using the improved flow-through cell method and the conventional paddle method. The pharmacokinetic characteristics of the immediate-release formulations were assessed in human subjects. The in vitro–in vivo correlation (IVIVC) was established based on the in vitro dissolution data and in vivo pharmacokinetic results. In vitro dissolution profiles were simulated into in vivo plasma concentration profiles using the GastroPlus® software. The improved flow-through cell method produced dissolution profiles that more closely aligned with in vivo results compared to the conventional paddle method. The similarity between in vitro and in vivo data was assessed using the f₂ similarity factor. The f₂ value for the conventional method was approximately 39.92, while the improved method showed values ranging from 52.64 to 80.47, exceeding the general equivalence threshold of 50 under all test conditions. These findings suggest that the improved dissolution method more accurately reflects in vivo drug behavior and may serve as a promising alternative to animal testing for evaluating immediate-release formulations.