alexa Abstract | Optimization of paclitaxel containing pH-sensitive liposomes by 3 factor, 3 level box-behnken design

Indian Journal of Pharmaceutical Sciences
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Research Paper Open Access

Abstract

The aim of this study was to investigate the combined influence of 3 independent variables in the preparation of paclitaxel containing pH-sensitive liposomes. A 3 factor, 3 levels Box-Behnken design was used to derive a second order polynomial equation and construct contour plots to predict responses. The independent variables selected were molar ratio phosphatidylcholine:diolylphosphatidylethanolamine (X 1 ), molar concentration of cholesterylhemisuccinate (X 2 ), and amount of drug (X 3 ). Fifteen batches were prepared by thin film hydration method and evaluated for percent drug entrapment, vesicle size, and pH sensitivity. The transformed values of the independent variables and the percent drug entrapment were subjected to multiple regression to establish full model second order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full model equation to derive a reduced model polynomial equation to predict the dependent variables. Contour plots were constructed to show the effects of X 1 , X 2 , and X 3 on the percent drug entrapment. A model was validated for accurate prediction of the percent drug entrapment by performing checkpoint analysis. The computer optimization process and contour plots predicted the levels of independent variables X 1 , X 2 , and X 3 (0.99, -0.06, 0, respectively), for maximized response of percent drug entrapment with constraints on vesicle size and pH sensitivity.

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Author(s): Smita Rane Bala Prabhakar

Keywords

Box-Behnken design, pH-sensitive, liposomes, optimization, paclitaxel

 
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