Extruded and spheronized beads containing Carbopolo® 974P to deliver nonelectrolytes and salts of weakly basic drugs

The purpose of the study was to explore the utilization of Carbopol (R) 974P, NF, resin in a bead dosage form manufactured by extrusion and spheronization. It was possible to prepare beads in this study by using calcium chloride to overcome the tack problem associated with wetted Carbopol((R)) 974P. The actives included both salts of weakly basic drugs (chlorpheniramine maleate and diphenhydramine hydrochloride) and nonelectrolytes (caffeine and dyphylline) which have a broad range of solubilities. Nonelectrolytes were released faster than the salts of weakly basic drugs. This is contrary to the behavior typically seen with a matrix system where the more soluble drug is released faster than a poorly soluble one. In the results of the present study, the solubility does not determine the drug release rate. Ionic interactions between the protonated amines of the salts and the carboxylates of the Carbopol resin are suggested to be the reason for the slower release of the salts of weakly basic drugs. Data from tack measurements confirm that this ionic interaction affects the behavior of the wetted Carbopol. In addition to the drug release profiles, bead average diameter, roundness, friability, and density were also determined. (c) 2006 Elsevier B.V. All rights reserved.