Design and in vitro evaluation of Eudragit-based extended release diltiazem microspheres for once and twice daily administrations: the effect of coating on drug release behavior

Abstract

The aim of this investigation was to develop an extended release formulation of diltiazem hydrochloride (DL) for once and twice-daily administration, based on Eudragit (Eud) RL and RS microspheres using emulsion solvent evaporation method. Methods: Formulations with different drug-polymer concentrations were produced and characterized in terms of yield, encapsulation efficiency (EE), particle size and surface morphology. The drug release and thermal behavior of microspheres were also investigated. Selected microspheres were then coated with Eud RS by continuous solvent evaporation method, in order to modify the microspheres properties and burst release. Results: According to the results, the EE was in the range of 56-93 % for uncoated microspheres. The mean particle size of microspheres was different from 470 to above 1000 µm, based on various formulation variables. No difference was observed between the mean size of particles prepared with Eud RL and Eud RS. Microspheres showed sustained release behavior which was affected by drug: polymer ratio as well as particle size. Coating the microspheres not only improved the EE values (82-92 %), but also reduced the mean dissolution rate (MDR) and also the burst release. Conclusion: Microspheres prepared with DL: Eud RL ratios of 1:3 and 1:4, showed the release profiles in accordance with the USP criteria for DL extended release product, for dosing every 12 and 24 h, respectively.