Alginate microspheres of isoniazid for oral sustained drug delivery

Abstract

In the present study, spherical microspheres able to prolong the release of INH were produced by a modified emulsification method, using sodium alginate as the hydrophilic carrier. The shape and surface characteristics were determined by scanning electron microscopy using gold sputter technique. Particle sizes of both placebo and drug-loaded formulations were measured by SEM and the particle size distribution was determined by an optical microscope. The physical state of the drug in the formulation was determined by differential scanning calorimetry (DSC). The release profiles of INH from microspheres were examined in simulated gastric fluid (SGF pH 1.2) and simulated intestinal fluid (SIF pH 7.4). Gamma-scintigraphic studies were carried out to determine the location of microspheres on oral administration and the extent of transit through the gastrointestinal tract (GIT). The microspheres had a smoother surface and were found to be discreet and spherical in shape. The particles were heterogeneous with the maximum particles of an average size of 3.719mum. Results indicated that the mean particle size of the microspheres increased with an increase in the concentration of polymer and the cross-linker as well as the cross-linking time. The entrapment efficiency was found to be in the range of 40-91%. Concentration of the cross-linker up to 7.5% caused increase in the entrapment efficiency and the extent of drug release. Optimized isoniazid-alginate microspheres were found to possess good bioadhesion (72.25+/-1.015%). The bioadhesive property of the particles resulted in prolonged retention in the small intestine. Microspheres could be observed in the intestinal lumen at 4h and were detectable in the intestine 24h post-oral administration, although the percent radioactivity had significantly decreased (t(1/2) of (99m)Tc=4-5h). Increased drug loading (91%) was observed for the optimized formulation suggesting the efficiency of the method. Nearly 26% of INH was released in SGF pH 1.2 in 6h and 71.25% in SIF pH 7.4 in 30h. No significant drug-polymer interactions were observed in FT-IR studies. Dissolution and gamma-scintigraphy studies have shown promising results proving the utility of the formulation for enteric drug delivery.