Preparation and evaluation of highly drug-loaded fine globular granules using a multi-functional rotor processor.

Abstract

The manufacture of highly drug-loaded fine globular granules eventually applied for orally disintegrating tablets has been investigated using a unique multi-functional rotor processor with acetaminophen, which was used as a model drug substance. Experimental design and statistical analysis were used to evaluate potential relationships between three key operating parameters (i.e., the binder flow rate, atomization pressure and rotating speed) and a series of associated micromeritics (i.e., granule mean size, proportion of fine particles (106-212 µm), flowability, roundness and water content). The results of multiple linear regression analysis revealed several trends, including (1) the binder flow rate and atomization pressure had significant positive and negative effects on the granule mean size value, Carr's flowability index, granular roundness and water content, respectively; (2) the proportion of fine particles was positively affected by the product of interaction between the binder flow rate and atomization pressure; and (3) the granular roundness was negatively and positively affected by the product of interactions between the binder flow rate and the atomization pressure, and the binder flow rate and rotating speed, respectively. The results of this study led to the identification of optimal operating conditions for the preparation of granules, and could therefore be used to provide important information for the development of processes for the manufacture of highly drug-loaded fine globular granules.