In this work, we present a formulation of Clopidogrel-beta-cyclodextrin lipid carrier which was developed for efficient incorporation and persistent release. A 3-factor, 2-level Box-Behnken design was used to optimize the process parameters including Cholesterol (A), Diethyl ether (B) and Poloxamer 188/Span 80 (1:3) (C). 6 dependent variables globule size, refractive index, controlled drug release after 12 hour, viscosity, gel strength and spreadability were measured as responses. Mathematical equations and response surface plots were used to relate the dependent and independent variables by using Design-Expert software (DX11).