An application of the computer optimization technique to wet granulation process involving explosive growth of particles

Abstract

The computer optimization technique based on well-designed experiments is applied to optimize the wet granulation process in which an explosive growth of particles is involved. Total volume of binder solution used in the process ( X 1), power consumption ( X 2) of the blade and the interaction between X 1 and the blade rotation speed ( X 3) were found to have strong influence on the granulation process based on the analysis of variance. Further, scraping off of powder adhered to the vessel wall by the blade could play a critical role in such explosive growth of particles. In scale-up studies (1.2 kg and 3.0 kg scale), an optimization incorporating scale effect of three response variables (geometrical mean size of granules, the portion of granules passed through 75 μm, and granulation time) which have high correlation coefficients in regression analysis was possible by using an integrated optimization function, T(X). A universal optimal condition unaffected by manufacturing scale is obtained by the minimization of T(X). Experimental values of these three response variables of granules prepared under the universal optimal condition agreed well with the predicted values in two manufacturing scales, suggesting that the computer optimization technique would be useful to optimize and visualize the process of wet granulation involving the explosive growth of particles.