Optimization of preparation method by W/O/W emulsion for entrapping metformin hydrochloride into poly (lactic acid) microparticles using Box-Behnken design

Abstract The aim of this study was to encapsulate an anti-diabetic drug (Metformin hydrochloride) within poly (lactic acid) microspheres, by using a double emulsion solvent evaporation method with different emulsifiers. Response surface methodology using Box-Behnken design was used to optimize the effects of fours factors (the amount of metformin in the inner aqueous phase (X 1 ), pH of the external aqueous phase (X 2 ), amount of polyvinyl alcohol as a surfactant in the external aqueous phase (X 3 ) and the stirring rate (X 4 )) on the encapsulation efficiency, particle size and zeta potential. The optimized microspheres hada spherical shape and exhibited zeta potential of −20.8 mV, average diameter of 271.41 μm and encapsulation efficiency of 78.05%. These values were reached by applying the following conditions: X 1  = 25 mg, X 2  = 4, X 3  = 1.5% and X 4  = 400 rpm. Differential scanning calorimetry and powder X-ray diffraction studies revealed that Metformin was present in an amorphous state in the microparticles. The study of the in-vitro drug release performed in simulated gastric and intestinal fluids showed that the drug release was more rapid with HPMC than with Span ® 80 emulsifier.