Solubilization of sirolimus using SNEDDS formulations: Application of statistical experimental design

Abstract

Purpose: The present study was aimed to statistically design, develop and evaluate an optimal SNEDDS formulation (SNEDDS: self-nanoemulsifying drug delivery systems) for solubilization of sirolimus using experimental design approaches to define the role of each formulation component and then to assess its physicochemical properties. Methods: Solubility measurements were carried out in pure vehicles. Response surface experimental design was applied to explore the effect of variables (amount of oil, surfactant and cosurfactant) on response (solubility of sirolimus in formulations). Selected formulations with the greatest solubilizing capacity were evaluated for their dissolution properties. The computer based optimization process predicts the amount of each component for yielding an optimized formulation. Results: Considering the combination of factor levels which maximizes solubility, increasing the amount of Transcutol and decreasing the amount of Chremophor RH 40 and Capryol PGMC could enhance the solubility of sirolimus in SNEDDS formulations. Droplet sizes of the formulations upon dilution were decreased as a result of increasing the proportion of surfactants. The optimized formulation showed a desirable solubilizing power (34.6 mg/ml) and a significant increase in the dissolution rate of the drug (74.15 % within 5 min). Conclusion: Statistical design is a useful tool to determine the effect of each component on the solubility of sirolimus and to obtain an optimized SNEDDS formulation with the greatest solublizing capacity, dissolution rate and desirable droplet size. © ECV. Editio Cantor Verlag, Aulendorf (Germany).