Preparation of Sustained Release Formulation of Verapamil Hydrochloride Using Ion Exchange Resins

The purpose of this investigation was to formulate and evaluate the interaction between cation exchange resins and verapamil hydrochloride. The uptake studies were conducted using the rotating bottle apparatus. The Langmuir-like equation was applied to the experimental data and the maximum drug loading was determined from the Langmuir-like parameters. The drug-resin complexes were evaluated using XRD, SEM, and particle size analysis. Release studies were performed using USP dissolution apparatus 2. The resin with the lowest percentage of cross-linking had the highest uptake capacity. The percent increase in particle size due to complexation was found to be associated with drug loading; the highest drug loading had the highest increase in particle size. The X-ray diffraction patterns of the resins and the drug-resin complexes showed that they were both amorphous. The maximum drug release was approximately 40% when conventional dissolution testing was used. Results showed that sink conditions could not be maintained using conventional dissolution methods. Maximum drug release increased dramatically by increasing the volume of samples withdrawn and fresh dissolution medium added. Excellent correlation was obtained between sample volume and drug release rate with an R-value of 0.988. Particle diffusion-controlled model and film diffusion-controlled model were both applied to the experimental data. The results indicated that the rate-limiting step is the diffusion of the exchanging cations through the liquid film. The modified release formulation was prepared successfully and correlated very well with the USP monograph for verapamil hydrochloride extended release capsules.

Automated summary

The study aimed to investigate the interaction between cation exchange resins and verapamil hydrochloride. Uptake studies showed that the resin with the lowest cross-linking had the highest uptake capacity. XRD, SEM, and particle size analysis confirmed the amorphous nature of the drug-resin complexes. Release studies demonstrated that conventional dissolution testing did not maintain sink conditions and that increasing the volume of samples withdrawn and fresh dissolution medium added significantly increased the drug release. The diffusion of exchanging cations through the liquid film was determined to be the rate-limiting step.