The present study investigated the ability of the in vitro transfer model and an in vivo pharmacokinetic study in rats to investigate the supersaturation and precipitation behaviour of albendazole (ABZ) relative to data from a human intestinal aspiration study reported in the literature. Two lipid based formulation systems, a hydroxypropyl-β-cyclodextrin (HPβCD) solution and the addition of a crystallization inhibitor (HPMC-E5) on the behaviour of ABZ was investigated. These formulations were investigated to represent differences in their ability to facilitate supersaturation within the small intestine. Overall, both the in vitro transfer model and the in vivo rat study were able to rank order the formulations (as aqueous suspension±HPMC<Lipid based formulations<HPβCD-solution) in accordance with the observations in the human aspiration study. The results therefore demonstrated that both the in vivo rat model and the in vitro transfer model could reflect the performance of the ABZ formulations in the human study. Whilst the rat was able to provide information on the overall plasma exposure, through the use of the in vitro transfer model, a more mechanistic understanding of the supersaturation and precipitation behaviour of ABZ using the different formulation strategies, could be attained.
Keywords: Albendazole; Lipid based formulations; Rat pk study; Supersaturation & precipitation; Transfer model; Weak base.
Copyright © 2017 Elsevier B.V. All rights reserved.