OPTIMIZATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) OF REPAGLINIDE USING D-OPTIMAL MIXTURE EXPERIMENTAL DESIGN

Abstract

Repaglinide, which is widely used in treatment of type 2 diabetes, is practically insoluble in water with low bioavailability (about 50%) and poor absorption characteristics in upper intestinal tract. Self-nanoemulsifying drug delivery system (SNEDDS) of repaglinide was developed and optimized using D-optimal mixture design to improve its dissolution and solubility. Suitable combination of excipients was selected by assessing solubility, emulsification efficiency and use of ternary phase diagram. The D-optimal mixture experimental design was applied to optimize formulation containing minimum amount of surfactant, maximum amount of lipid showing enhanced emulsification and dissolution rates. Four formulation variables; the oil phase X1 (Labrafil^® M1944CS) and X2 (Capmul^® MCM-C8), the surfactant X3 (Tween^® 80) and the co-surfactant X4 (Transcutol^® P) were used in the design. The prepared eleven formulations were evaluated in vitro for droplet size and % drug release. Formulation F5 was found to be optimum showing 100.05% drug release 53 nm droplet size, 13 s self-emulsification time and robustness to dilution with different media.

KEYWORDS: Repaglinide, SNEDDS, D-optimal design, Poorly water soluble drug