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

作者：Mukherjee Tusharmouli; Plakogiannis Fotios M^*

来源：Journal of Pharmacy and Pharmacology, 2010, 62(9): 1112-1120.

DOI：10.1111/j.2042-7158.2010.01149.x

• albendazole
• bioavailability
• D-optimal design
• microemulsion
• self-microemulsifying drug delivery system (SMEDDS)

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 (C(max)) 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.

• 出版日期2010-9