Drug release from film-coated chlorpheniramine maleate nonpareil beads: water influx and development of a new drug release model.

The purpose of this work was to investigate drug release from film-coated chlorpheniramine maleate (CPM) nonpareils (sugar spheres) and the effect of water influx on the drug release mechanism. The methods used in the study involved the layering of CPM onto nonpareil cores using a fluid-bed apparatus. These CPM cores were then coated with an aqueous ethylcellulose dispersion, which was blended with a solution of hydroxylpropylmethylcellulose (HPMC) at different concentrations. The net water influx was determined by measuring water uptake during dissolution. The film surface area was calculated from bead diameters measured with an optical microscope. Drug release profiles were measured using USP dissolution method I (basket). The results showed that significant water influx occurred, which produced an internal liquid phase ranging from 0 to 1.8 x 10(3) mm3/g of sample. As a result of the water uptake, an increase in bead size was observed. The bead surface area varied over the range of 40-80 x 10(3) mm2/g sample because of a combined effect of the water uptake and the release of the bead contents. A bead geometry parameter was proposed as the ratio of the bead surface area to the volume of the internal liquid phase. This bead geometry parameter was measured as a function of time and fit to an equation using a computer curve-fitting technique. This equation was substituted into an existing drug release model to give a more appropriate mathematical model describing drug release from this system. The conclusion drawn from these results is that the influx of water during drug dissolution creates a progressive increase in the liquid phase within the nonpareil bead; this causes a corresponding increase in the bead surface area which influences the drug release rate.