Tusharmouli Mukherjee1, Fotios M Plakogiannis. 1. Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA. tmouli@hotmail.com
Abstract
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.
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.
Authors: Dong Woo Yeom; Ye Seul Song; Sung Rae Kim; Sang Gon Lee; Min Hyung Kang; Sangkil Lee; Young Wook Choi Journal: Int J Nanomedicine Date: 2015-06-05