Formulation and process considerations for beads containing Carbopol (R) 974P, NF resin made by extrusion-spheronization

Preliminary studies revealed that Carbopol(R) 974P, NF resin could be incor porated into beads manufactured by extrusion and spheronization, and can sl ow the release of a highly water soluble drug if calcium chloride was inclu ded in the granulating fluid to reduce the tack of the wetted polymer. In t his study, the same approach was used to produce high quality chlorpheniram ine maleate beads with a prolonged release duration. Because of the complex nature of the extrusion and spheronization process and the various compone nts in the bead formulations, a statistically sound factorial experiment wa s considered for this study. A one-half fraction of a two level factorial d esign with three center points was employed to estimate the effects of simu ltaneously modifying multiple process and formulation variables, including the Carbopol(R) concentration, calcium chloride concentration, water conten t, and the spheronization speed and time. Product yield, average bead round ness, and the drug release profile were selected as responses. Increasing t he Carbopol(R) content across the experimental range resulted in a signific ant (P<0.05) reduction in the percentage drug released at 25, 40, and 60 mi n. Results suggest that combining the conditions of high Carbopol(R), high water, and low calcium chloride levels with low spheronization speeds at lo ng spheronization times produce the highest quality bead with the longest d rug release duration. (C) 2000 Elsevier Science B.V. All rights reserved.