Formulation and development of nateglinide loaded sustained release ethyl cellulose microspheres by O/W solvent emulsification technique

Abstract

The aim of this study was to investigate the combined influence of 3 independent variables in the preparation of sustained release Nateglinide (NTG) microspheres by O/W solvent emulsification method. A 3-factor, 3-level Box–Behnken design was used to derive second order polynomial equation and construct contour plots to predict responses. The independent variables selected were polymer concentration (A), surfactant concentration (B) and speed of the stirrer (C). Percentage drug loading (Y1) and Percentage drug release (Y2) were considered dependent variables. The prepared microspheres were evaluated for percentage of yield, drug loading, drug release study in 6.8 phosphate buffer, Fourier transform infrared (FT-IR), X-ray diffraction (XRD), scanning electron microscopy analysis. Contour plots were constructed to show the effects of of A, B, C on Y1 and Y2. The yield of microspheres was found to be in the range of 42.29–97.22 %. The drug loading was found to be in the range of 12.18 % (F9) to 24.55 % (F14). FT-IR analysis revealed no drug excipient interference. The morphology of evaluated microspheres were found to be spherical and smooth in nature. In XRD analysis crystalline pattern of pure NTG was changed to amorphous pattern when converted to microspheres. Out of 17 batches, formulation batches F1, F4, F12, F14, F17 had percentage drug loading 52.75, 50.78, 43.88, 47.45, 44.78 % at 10 h respectively which indicated excellent sustained drug release pattern. From this study it was concluded that NTG loaded ethyl cellulose sustained release microspheres were developed using 3-factor, 3-level Box–Behnken design.