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


RESULTS
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.
Mukherjee
Tusharmouli
T
Division of Pharmaceutical Sciences, Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA. tmouli@hotmail.com
Plakogiannis
Fotios M
FM
D000284:Administration, Oral; D015766:Albendazole / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002210:Caprylates; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000592:standards; D004655:Emulsions; D005260:Female; D005989:Glycerides; D019999:Pharmaceutical Solutions / Q000592:standards; D011092:Polyethylene Glycols; D011136:Polysorbates; D011817:Rabbits; D012995:Solubility
D002210:Caprylates; D004655:Emulsions; D005989:Glycerides; D019999:Pharmaceutical Solutions; D011136:Polysorbates; C022131:cremophor; D011092:Polyethylene Glycols; D015766:Albendazole; C025343:monooctanoin