Preparation of diltiazem HCl-modified release formulation using cation-exchange resin as a single excipient.

Abstract

Objective: Modified released formulations of diltiazem were previously prepared using cation-exchange resins. However, multiple excipients were required to achieve the appropriate release rate. It was of interest to prepare a modified release dosage form of diltiazem using drug-resin complex alone.

Methods: Adsorption experiments conducted using a rotating bottle apparatus. The procedure involved adding the resin to the bottles, followed by appropriate amount of drug solution. The bottles were rotated until equilibrium was reached and the concentrations were analyzed using a reversed phase HPLC method, which effectively separated the compound from its degradation product. Release studies were conducted using a USP dissolution apparatus 2 with phosphate buffer as the dissolution medium.

Key findings: Diltiazem was unstable inside the resin when the H⁺ form was used. It became stable when the H⁺ was displaced with Na⁺. Langmuir-like equation was applied to the adsorption isotherms. The equation parameters were influenced by the resin's cross-linking and particle size. Maximum drug release is related to sample volume. Positive linear relationship was obtained between initial release rate and extent of uptake.

Conclusion: This study successfully demonstrates that Dowex® 50WX8 (Na⁺ form) can be used as a single excipient in diltiazem formulations, providing both chemical stability and sustained release without requiring additional polymer coatings.