Development of Sustained Release Eudragit Based Matrix Tablet of Fluvastatin Sodium Microspheres

Abstract

The purpose of this research is to investigate the suitability of acquiring improved dissolution profile and sustained release of Fluvastatin sodium to reduce dosage frequency via a novel combination of freeze dried microspheres and Eudragit polymers-based matrix tablet technologies. Fluvastatin sodium microspheres were prepared using polyvinyl pyrollidone K-30 and Poloxamer 407 through solvent evaporation via freeze drying. We adopted a central composite design to examine the influence of independent variables viz. drug:polymer (X1) and surfactant (X2) on the t50 % (Y1), Q90 (Y2) and percentage drug content (Y3) along with determination of an optimized composition for production of an optimal Fluvastatin sodium microspheres. Design expert software illustrated that an optimized Fluvastatin sodium microspherescould be achieved using 1:3.496 drug:polymer and 3.102 % poloxamer 407 which would illustrates t50 % (36.33 min), Q90 (79.99 %) and percentage drug content (81.589 %). The mean diameter and polydispersity index of Fluvastatin sodium microspheres using dynamic light scattering was found 0.78 μm and 0.287, respectively. Sustained release tablet of optimized Fluvastatin sodium microspheres (Fluvastatin sodium microspheres-sustained release tablet) was manufactured using Eudragit RS 100 and Eudragit RL 100 based granules by wet granulation technique. In vitro drug release kinetics studies were executed to assess the drug release mechanism from optimized Fluvastatin sodium microspheres and Fluvastatin sodium microspheres-sustained release tablet. The dissolution level of Fluvastatin sodium was 3.58-fold improved wthin 2 h through the freeze dried microspheres. Fluvastatin sodium microspheres-sustained release tablet showed sustained drug release over 24 h and was matched properly to Korsmeyer-Peppas model with release exponent of 0.5318, which indicated drug release through diffusion and erosion mechanism. Conclusively, it has been demonstrated that novel combination of freeze dried microspheres and their Eudragit polymers-based matrix tablet techniques could find great potential for improving drug dissolution and sustained release of water insoluble drugs along with reduced dosage frequency.