OPTIMIZATION OF FORMULATION PARAMETERS FOR PREPARATION OF DOCETAXEL LOADED NANOSTRUCTURED LIPID CARRIERS

Present paper explores the preparation of Nanostructured Lipid Carriers (NLCs) loaded with the anticancer agent docetaxel trihydrate, with potential for targeted anticancer drug delivery. NLCs were prepared using Melt Emulsification Solvent Evaporation – Sonication method. The procedure adopted for preparation was optimized for obtaining NLCs with high entrapment efficiency for the drug and particle size in suitable range, using Quality by Design (QbD) approach employing Design-Expert® software. NLCs were prepared using solid lipids (stearylamine and glycerylmonostearate) and liquid lipids (tocopheryl acetate) with the aid of PhospholiponS100® as emulsifier and LutrolF68® as stabilizer.  Independent variables selected were {total lipid to drug ratio} (A) and {solid lipids to liquid lipid ratio} (B). Total lipid to drug ratio (A) was fixed at four levels whereas solid lipid to liquid lipid ratio (B) was fixed at three levels. Optimization batches were prepared in duplicates and entrapment efficiency and mean particle size of each batch was estimated and data analyzed for statistical significance through ANOVA and by response surface and contour plots. The optimized batch identified was found to have desirability value of 0.955 and total lipid to drug ratio and solid to liquid lipid ratio of 20:1 and 2:1 respectively. Resultant particles were found to have average size of 175-180nm with low polydispersity, zeta potential in the range of 55-65mV and had 4.7-4.9%w/w of loaded drug which corresponded to an entrapment efficiency of 98-99%w/w. DSC and SEM studies confirmed amorphization and molecular solubilization of docetaxel in NLC and nearly spherical shape of NLCs respectively.