Formulation and in-vitro evaluation of novel starch-based tableted microspheres for controlled release of ampicillin

Abstract

This study reports the preparation of starch-based tableted microspheres that are crosslinked with epichlorohydrin (EPI) using a modified water-in-oil (w/o) emulsification technique. Ampicillin (AMP), a broad spectrum antibiotic was encapsulated up to the extent of 70% into the microspheres. The microspheres were characterized by Fourier transform infrared spectroscopy (FT-IR) to confirm the crosslinking reaction and chemical stability of AMP. Differential scanning calorimetry (DSC) was studied on the placebo and drug-loaded microspheres to confirm the polymorphism of AMP. Results of this study indicated a molecular level dispersion of AMP in the developed microspheres. Scanning electron microscopy (SEM) confirmed the spherical nature and smooth surfaces of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering ranged between 96 and 158 μm. Diffusion coefficients ( D) of water transport through the microspheres were determined using an empirical equation. Values of D decrease with increasing crosslinking as well as increasing content of starch in the microspheres. In-vitro release studies were performed in 1.2 and 7.4 pH media to simulate the gastric and intestinal conditions. The results indicated a dependence on the amount of polymer and extent of crosslinking. Release data were fitted to an empirical relation to estimate transport parameters and to understand the transport mechanism. Statistical analyses of release data was performed using analysis of variance (ANOVA) method. Suitable microspheres were selected and compressed into tablets using the directly compressible excipients. SEM photographs of the fractured part of the tablet revealed the presence of discrete microspheres in the tablets, suggesting that the system chosen is ideal for tableting. Tablets significantly lowered the initial burst effect when compared to microsphere formulations. The tablets were effective in releasing the AMP over an extended period of about 24 h.