SIMULTANEOUS-OPTIMIZATION OF WET GRANULATION PROCESS INVOLVING FACTOROF DRUG CONTENT DEPENDENCY ON GRANULE SIZE

Computer optimization technique was applied to the simultaneous optimi zation of wet granulation process by a high-speed miser granulator. Fo ur pharmaceutical properties, including yield, drug content uniformity , geometrical mean diameter of granules, and uniformity of granule siz e, were selected to evaluate the quality of the granules. In particula r dependence of drug content uniformity on granule size was investigat ed using two model drugs, ascorbic acid and ethenzamide. An appreciabl e dependence of ascorbic acid content on granule size was not observed in model formulations. On the other hand, ethenzamide was contained m ore in small-size granules, and its content was decreased with an incr ease in amounts of hydroxypropyl cellulose (HPC-L; used as a binder) a nd binder solution. These observations suggested that drug content uni formity is influenced not only by drug solubility in the binder soluti on, bur also by the use of HPC-L. A simultaneous optimal point incorpo rating four pharmaceutical properties was obtained using the generaliz ed distance function. The experimental values of the foul response var iables obtained in newly prepared granules were found to correspond we ll with the predicted values of both granules containing ascorbic acid and ethenzamide. These results suggested that computer optimization w ould benefit the wet granulation process even if drug content segregat ion was involved in the process. Further, data obtained from computer optimization, in particular the contour diagram, will be valuable in t he process validation.