Donepezil Hydrochloride BCS Class Ambiguity: Relevant Aspects to be Considered in Drug Classification.

Donepezil hydrochloride (DH) is the most used anti-Alzheimer's disease drug, however, its classification according to the Biopharmaceutics Classification System (BCS) is not clear in the literature. BCS is one of the accepted criteria used to grant biowaiver (waiver of in vivo bioequivalence studies) of new drug products. So, the purpose of this work was to elucidate the BCS classification of DH and to raise the discussion about the possibility of biowaiver for new medicines containing it. The polymorphic form was previously identified as form III of DH. The drug showed high solubility in the entire pH range evaluated (1.2 to 6.8, at 37 °C) with a pH-dependent solubility profile. The effective permeability (P) values obtained with different DH concentrations, using in situ closed-loop perfusion model were statistically similar (p > 0.05), even when compared to high permeability control used (ketoprofen), demonstrating that DH has high permeability which, associated with its high solubility, allows to classify DH as BCS class 1. Relevant data to evaluate for granting a biowaiver for new medicines were also reviewed from the literature. Based on information reunited new immediate-release drug products containing DH should be eligible for BCS-based biowaiver.