The Impact of Surface Area per Volume (SA/V) Ratio on Drug Transport from Supersaturated Solutions of Ketoconazole

Eur J Pharm Biopharm. 2023 May 16:S0939-6411(23)00138-8. doi: 10.1016/j.ejpb.2023.05.016. Online ahead of print.ABSTRACTThe purpose of this study aimed to evaluate the impact of the surface area per volume (SA/V) ratio on drug transport from two supersaturated solutions (SSs) of ketoconazole with and without hydroxypropyl methylcellulose (HPMC), used as a precipitation inhibitor. In vitro dissolution, membrane permeation with two SA/V ratios, and in vivo absorption profiles for both SSs were determined. For the SS without HPMC, a two-step precipitation process due to the liquid-liquid phase separation was observed; the constant concentration with approximately 80% of the dissolved amount was maintained for the first 5 min and subsequently decreased between 5 and 30 min. For the SS with HPMC, a parachute effect was observed; the constant concentration with approximately 80% dissolved amount was maintained for more than 30 min and decreased very slowly thereafter. Assessment of the SA/V ratio using in vitro and in vivo models demonstrated that when the SA/V ratio was small, the SS with HPMC resulted in a significantly higher permeated amount than the SS without HPMC. In contrast, when the SA/V ratio was large, the HPMC-mediated parachute effect on drug transport from SSs was attenuated, both in vitro and in vivo. The parachute effect by HPMC decreased as the SA/V ratio increased, and the performance of supersaturating formulations would be overestimated by in vitro studies with...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Source Type: research