Multiple-unit sustained release tablets of film-coated diltiazem hydrochloride resinates

Abstract

The objective of this study was to prepare the multiple-unit sustained release tablet of film-coated diltiazem hydrochloride resinates. Diltiazem hydrochloride (DTZ) was loaded in sulfonic acid cation exchange resins, Dowex® 88 4% crosslinkage and Dowex®HCR-S 8% crosslinkage by batch method. The factors affecting drug loading were investigated such as resin crosslinkage, quantity of resins, drug loading solution concentration and temperature during drug loading process. The DTZ bound in 4 % crosslinkage resins was 28.80 % which was higher than in an 8 % crosslinkage resin which was only 5.51 %. The percentage of DTZ loading in the resins decreased when the quantity of resins in the drug loading solution was increased. The drug resin in the ratio of 1:1 in 8 % w/v drug loading solution was suitable for preparing resonates. Increasing in temperature increased the percentage of DTZ loading and reduced the time required for system to reach equilibrium. The resinates could prolong DTZ release over 12 hours in 0.1 M potassium chloride solution. The release kinetic of resinates was best described by the matrix-diffusion controlled model (Higuchi model). The release rate was influenced by the ionic strength of dissolution medium, while the pH of dissolution medium did not .To modify drug release from resinates, they were coated with acrylate polymer by using fluidized bed coating technique. Coating with 7.5-15 % coating level of Eudragit®RL and Eudragit®RS decreased the drug release rate but did not affect the drug release kinetic. Coated resinates were formulated into disintegrating tablets and compressed at compression pressure between 340-1,022 pounds. Tablets formulated using microcrystalline cellulose and polyethylene glycol 4000 exhibited good physical properties. Drug release of resinate before and after formulated into disintegrating tablets was similar. The release kinetic of drug from disintegrating tablets was also described by Higuchi model.