Development and oral bioavailability assessment of a supersaturated self-microemulsifying drug delivery system (SMEDDS) of albendazole

摘要

Objectives Albendazole's (ABZ) poor aqueous solubility is a major determinant of its variable therapeutic response (20-50%). The purpose of this study was to develop and optimize the composition of a self-microemulsifying drug delivery system (SMEDDS) of ABZ and assess its oral pharmacokinetics in rabbits. Methods A D-optimal mixture design of experiments was used to select the levels of constraints of the formulation variables. The predicted composition was optimized using four responses: dispersion performance, droplet sizes, dissolution efficiency (DE) and time for 85% drug release (t 85%). Key findings The optimal composition of the ABZ-SMEDDS formulation, with approximately 5 mg/g drug loading of ABZ, was predicted to be Cremophor EL (30% w/w), Tween 80 (15% w/w), Capmul PG-8 (10% w/w) and acidified PEG 400 (45% w/w). An increase of 63% in the relative bioavailability compared with the commercial suspension was obtained with ABZ-SMEDDS as measured by albendazole sulfoxide (ABZSO) plasma levels. The area under the curve (AUC 0→24h) and the peak plasma concentration (Cmax) of ABZ-SMEDDS was higher than those obtained with the commercial suspension by 56% and 52%, respectively. Conclusions This study demonstrates a strategy for the development of a supersaturated SMEDDS formulation of a drug with low aqueous solubility.