Formulation design and experiment interpretation through torque measurements in high-shear wet granulation

High-shear wet granulation is commonly used in many industries such as in the pharmaceutical one to convert fine cohesive powders into dense and round granules. The purpose of this work was to determine the effects of some important powder properties (crystalline or amorphous nature, hygroscopicity, solubility and particle size) and process variables (liquid addition rate, impeller speed) on the early stages of the granulation process and on drug distribution in granules obtained by high shear wet granulation. The glass transition concept coupled with on-line impeller torque monitoring and measurements of the time evolution of the particle size distribution were used to study mixtures of pharmaceutical excipients and some common active ingredients. In particular a formulation map for estimating the minimum amount of liquid binder required to induce appreciable granule growth is presented outlining therefore a new method to considerably increase the predictability of the behaviour of different formulations on the basis of the physical properties of each single component. The description of the effects of wetting condition on drug uniformity content in some formulation with hydrophobic actives is given as well.