Development of diltiazem hydrochloride controlled release pellets : effect of drug concentrations and encapsulating polymers on kinetic and release

Abstract

The high dose (90 mg/150 mg) of diltiazem hydrochloride (DTZ HC1) pellets were prepared by extrusion-spheronization process. Core pellets which provided the most spherical shape containing DTZ HC1 and Avicel PH 101 60:40 percent w/w and using HPC-M 0.5 percent by weight on dry substance as binder solution were selected. The other doses of DTZ HC1 pellets were also prepared and found that rough surface pellets occured in low dose (30 mg/150 mg), due to the shrinking property of high level of Avicel PH 101. Triethyl citrate 20 percent based on weight of ethylcellulose polymer was used as plasticizer in coating film due to the results of optimum film strength, flexibility, toughness and drug release characteristic with simple using in coating process. For dissolution study, the drug pellets were coated with 7.5 percent w/w coating level and mixed with uncoated pellets as an initial dose at the ratio of 4:1 gave an insignificant release to Herbesser 90 SR in medium as described by USP 23 and pH changed medium. The release mechanism was studied with various doses of DTZ HC1 coated pellets range from 30, 45, 60 and 90 mg. The release profiles of 30 and 45 mg/doses can be divided into three phases as lag time, constant release and declining rate period. However, at 60 and 90 mg/dose, only lag time and constant release periods occurred. Thus, it can be concluded from the release mechanism that diffusion may be involved during lag time period and the driving force in constant release period probably comes from the swelling force of Avicel PH 101 with 0.5 percent HPC-M and osmotic pressure produced from DTZ HC1 which acts as osmotic inducing agent.