PURPOSE: To develop and evaluate the in vitro/in vivo performance of diltiazem sustained release pellets that were prepared by the Wurster column process. METHODS: Pellets containing diltiazem were prepared by spraying a slurry of micronized diltiazem hydrochloride, pharmaceutical glaze and alcohol onto an appropriate mesh fraction of nonpareil seeds using the Wurster column. A two-step drug layering process was used to increase drug loading from 60% to 75%. The oven-dried diltiazem basic pellets were coated with ethylcellulose/dibutyl sebacate coating solution to yield diltiazem sustained release pellets. An open, randomized Latin square, three-way crossover clinical study was used to evaluate the in vivo performance of the coated product. RESULTS: Altering the mesh fraction of the starting nonpareil seeds for this layering process was found to affect the release characteristics of drug from the pellets. An oven-drying step was required to stabilize the diltiazem basic pellets. The thicker the drug loading layer the longer the oven drying is needed to stabilize the pellets. The diltiazem sustained release pellets produced by these methods displayed sustained release dissolution profiles both in vitro and in vivo. Diltiazem basic pellets coated with a 0.6% ethylcellulose/dibutyl sebacate coating showed a different rate of absorption (lower Cmax and higher Tmax) and the same extent of absorption as compared to Cardizem tablets. CONCLUSIONS: Clinical data confirmed that this formulation approach is an effective means to produce a diltiazem sustained release product.
RCT Entities:
PURPOSE: To develop and evaluate the in vitro/in vivo performance of diltiazem sustained release pellets that were prepared by the Wurster column process. METHODS: Pellets containing diltiazem were prepared by spraying a slurry of micronized diltiazem hydrochloride, pharmaceutical glaze and alcohol onto an appropriate mesh fraction of nonpareil seeds using the Wurster column. A two-step drug layering process was used to increase drug loading from 60% to 75%. The oven-dried diltiazem basic pellets were coated with ethylcellulose/dibutyl sebacate coating solution to yield diltiazem sustained release pellets. An open, randomized Latin square, three-way crossover clinical study was used to evaluate the in vivo performance of the coated product. RESULTS: Altering the mesh fraction of the starting nonpareil seeds for this layering process was found to affect the release characteristics of drug from the pellets. An oven-drying step was required to stabilize the diltiazem basic pellets. The thicker the drug loading layer the longer the oven drying is needed to stabilize the pellets. The diltiazem sustained release pellets produced by these methods displayed sustained release dissolution profiles both in vitro and in vivo. Diltiazem basic pellets coated with a 0.6% ethylcellulose/dibutyl sebacate coating showed a different rate of absorption (lower Cmax and higher Tmax) and the same extent of absorption as compared to Cardizem tablets. CONCLUSIONS: Clinical data confirmed that this formulation approach is an effective means to produce a diltiazem sustained release product.