Formulation and optimization of ethosomes loaded with ropinirole hydrochloride: Application of quality by design approach

Abstract

The objective of the present study was to formulate and understand ethosomal formulations of Ropinirole (ROP) using quality by design (QbD) approach. To assess the effect of independent variable such as soya phosphatidyl choline and ethanol concentration on dependable variable such as vesicle size and percentage entrapment efficiency, a 32 factorial design were employed. Ethosomes were prepared by cold method and evaluated for the following parameter; vesicle size, zeta potential, polydispersity index and percentage entrapment efficiency. In vitro drug release of optimized formulation was performed and compare with pure drug solution. Based on QbD approach, design space (DS) was optimized with a combination of selected variables with entrapment efficiency > 50% w/w and a particle size < 400 nm. The results of multivariate regression analysis illustrated that vesicle size and % entrapment efficiency of ethosomes were affected by ethanol concentration and phosphatidyl choline amount. The optimized formulation had ethanol concentration of 49.9% and Soya phosphatidyl choline amount 380 mg with vesicle size of 320.45 nm and entrapment efficiency of 65.69 ± 3.5%. In vitro drug release after 24 h from optimized formulation was found to be 64.8% when compared to pure drug which released 99.2% within 2 h. The conclusion of the study substantiates that by using a QbD approach, the effect of formulation variation in responses can be easily found based on the knowledge gained by regression analysis, the concept of ‘‘desirability function”.