Optimization of Formulation Parameters of Cytarabine

In the present study, 3 factorial design was used to investigate the combined influence of three independent variables in the preparation of Cytarabine liposomes by thin film hydration method. The process variables like rotation speed, temperature, vacuum applied and hydration time were kept constant through out the study. The formulation variables, Drug (Cytarabine) / Lipid [Phosphatidyl choline (PC) and Cholesterol (Chol)] molar ratio (X1), PC / Chol in percent ratio of total lipids (X2) and the volume of hydration medium (X3) were selected as the independent variables. Based on the factorial design, twenty seven batches of cytarabine liposomes were prepared. The liposome batches were evaluated for its drug entrapment within the liposomal vesicles. The percent drug entrapment (PDE) was selected as the dependent variable. The transformed values of independent variables were subjected to multiple regression analysis to establish a second order polynomial equation (full model). FStatistic was applied to establish a reduced polynomial equation (reduced model) by neglecting the nonsignificant (P > 0.01) terms from the full model. Based on the coefficient values obtained for independent variables from the regression equation, it was clear that the drug/lipid molar ratio (X1), which was having the maximum value (b1 = 5.36) was the major contributing variable for PDE within the liposomes. The reduced polynomial equation was used to plot three two-dimensional contour plots at a fixed levels of -1, 0 and 1 of the variable X3 to obtain various combination values of the two other independent variables (X1 and X2) at predetermined PDE. The established equation was validated by preparing three batches three times taking values of independent variables from the contour plots for the prefixed value of PDE. Response surface curves were also plotted to show the effects of X1, X2 and X3 on the PDE within liposomes. Thus the derived equation, response surface plots and contour plots helps in predicting the values of the independent variables for maximum PDE in the preparation of cytarabine liposomes by thin film hydration method.