Application of central composite design for optimization of spray dried fenbendazole- polyvinyl alcohol microparticles.

EVA CAROLINA ARRUA; CLAUDIO J. SALOMON

Rosario

Congreso; 4ta Reunión Internacional de Ciencias Farmacéuticas; 2016

Application of central composite design for optimization of spray dried fenbendazole- polyvinyl alcohol microparticles.Arrua E.1, Salomon C.1,2 arruacarolina@gmail.com1IQUIR-CONICET, Rosario, Argentina. 2Área Técnica Farmacéutica, Departamento Farmacia.Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR.This work describes the development of a methodology for optimizing fenbendazole (FNZ)-polyvinyl alcohol (PVA) microparticles prepared by spray drying process. FNZ (Methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is a crystalline powder insoluble in water and slightly soluble in most of the organic solvents. It is widely used to eliminate certain gastrointestinal parasites from the stomach and intestines of animals. However, due to its poor aqueous solubility, FNZ exhibit an erratic and extremely low oral bioavailability. Thus, the aim of this work was to formulate PVA-based microparticles by means of spray drying processes in order to increase FNZ solubility and dissolution rate. A preliminary analysis using Plackett-Burman design was applied to reduce the number of experiments and to analyze the factors (PVA %, Sipernat %, pump potency, and inlet temperature) which would have a significant effect on three responses (yield, drug loaded, and drug solubility). Sipernat is silica with high absorption capacity that enhances flowability and prolongs the shelf life of powdered substances which are liable to caking. After analyzing the dependent and independent variables, a further optimization process by means of a central composite design-response surface methodology was undertaken to obtain the optimal formula of FNZ microparticles. Responses were fitted to polynomial patterns to find the best models. ANOVA results of responses exhibited good statistical indicators, lack of fit was not significant, model was significant and adjusted and predicted R2 were similar. These results showed that the linear model was appropriate to explain the yield and amount of FNZ loaded, while FNZ aqueous solubility was well fitted to a quadratic model. Test with the highest desirability obtained (0.8139) was selected. In these conditions, the microparticles were formulated using 0.5g PVA and 50ml Sipernat solution. The parameters of the process were: spray pump in 12 and a temperature of 131°C. Optimized FNZ microparticles were obtained with a yield of 78% and the amount of drug in the final solid was 189μg/mg. Moreover, the FNZ aqueous solubility increased up to 144μg/ml, while the FNZ solubility is 2.57.10-3μg/ml.