A novel calcium silicate based microspheres of repaglinide: in vivo investigations

The objective of the present investigation was to evaluate gastro-retentive performance and pharmacokinetic parameters of optimized floating microspheres (RgFMCS4) consisting of (i) calcium silicate (CS) as porous carrier; (ii) repaglinide (Rg), an oral hypoglycemic agent; and (iii) Eudragit S (ES) as polymer. The optimized formulation demonstrated favorable in-vitro-floating and drug release characteristics. The gastro-retentive behavior of this optimized formulation was compared with non-floating microspheres (RgNFM) prepared from the identical polymer. Stability test of (99m)Tc-labeled formulations were carried out using appropriate standard buffer solutions of pH 2.0, 6.8 and 7.4. The organ distribution study was performed in albino rats in order to measure labeling efficiency of the formulation with (99m)Tc. The gamma scintigraphy of the formulations was carried out in albino rabbits to monitor the transit of RgFMCS4 and RgNFM in the gastrointestinal (GI) tract. Prolonged gastric residence time (GRT) of over 6 h was achieved in all animals for calcium silicate based floating microspheres of Rg. Rg loaded optimized formulation was orally administered to albino rabbits and blood samples were used to determine pharmacokinetic parameters of Rg from floating microspheres, which were compared with pharmacokinetic parameters of the marketed tablet formulation. The relative bioavailability of Rg loaded floating microspheres was found to be increased about 3.17 times in comparison to that of the marketed tablet. The enhanced bioavailability and eliminated half-lives of Rg formulation observed in the present study are attributed to the floating nature of the designed formulations.