Scale-up studies on high shear wet granulation process from mini-scale to commercial scale.

A newly developed mini-scale high shear granulator was used for scale-up study of wet granulation process from 0.2 to 200 L scales. Under various operation conditions and granulation bowl sizes, powder mixture composed of anhydrous caffeine, D-mannitol, dibasic calcium phosphate, pregelatinized starch and corn starch was granulated by adding water. The granules were tabletted, and disintegration time and hardness of the tablets were evaluated to seek correlations of granulation conditions and tablet properties. As the granulation proceeded, disintegration time was prolonged and hardness decreased. When granulation processes were operated under the condition that agitator tip speed was the same, similar relationship between granulation time and tablet properties, such as disintegration time and hardness, between 0.2 L and 11 L scales were observed. Likewise, between 11 L and 200 L scales similar relationship was observed when operated under the condition that the force to the granulation mass was the same. From the above results, the mini-scale high shear granulator should be useful tool to predict operation conditions of large-scale granulation from its mini-scale operation conditions, where similar tablet properties should be obtained.