Design and In Vitro Evaluation of Eudragit-Based Extended Release Diltiazem Microspheres for Once- and Twice-Daily Administration: The Effect of Coating on Drug Release Behavior

Abstract
Objectives:
This study aimed to develop an extended-release formulation of diltiazem hydrochloride (DL) for once- and twice-daily dosing. The formulation was based on Eudragit RL and RS microspheres, prepared using the emulsion solvent evaporation method.

Materials and Methods:
Microsphere formulations were created with varying drug-to-polymer ratios and characterized for production yield, encapsulation efficiency (EE), particle size, and surface morphology. Drug release profiles and thermal behavior were also evaluated. To further modify their properties and reduce burst release, selected microspheres were coated with Eudragit RS via continuous solvent evaporation.

Results:
Encapsulation efficiency of the uncoated microspheres ranged from 56% to 93%. Depending on the formulation parameters, the average particle size varied between 470 μm and over 1000 μm. No significant size difference was observed between microspheres made with Eudragit RL and RS. All microspheres demonstrated sustained-release characteristics, influenced by both the drug-to-polymer ratio and particle size. Coating the microspheres enhanced EE (82%–92%) and further decreased both the mean dissolution rate and initial burst release.

Conclusion:
Microspheres with DL:Eudragit RL ratios of 1:3 and 1:4 met the USP standards for USP25/28 inhibitor AZ1 extended-release diltiazem formulations, suitable for 12-hour and 24-hour dosing intervals, respectively.