Material Physical Modifications Induced by Wet Granulation

Abstract Mechanical and solvent stresses in wet granulation can induce physical changes in the drug substance or excipients undergoing granulation. These physical changes can be in the form of solid state transformation such as polymorphic change, salt disproportionation, or hydrate formation. Micromeritic (particle structure/property changes) also can take place during wet granulation. Partial transformation of anhydrous lactose to lactose monohydrate in high shear wet granulation is an example of solid state transformation. Despite form conversion of anhydrous lactose to lactose monohydrate during wet granulation, it retains its inherent particle morphology, surface area, and porosity. The higher compactibility of anhydrous lactose was maintained after wet granulation, indicating that particle structure, and not crystal structure, is the factor governing performance of lactose in compaction. The decrease in MCC particle porosity by wet granulation is an example of micromeritic changes in wet granulation. The decrease in MCC primary particle porosity resulted in the decrease in MCC compactibility even without significant particle size growth. Aggregation of MCC particles into large dense granules when the binder is included in the formulation resulted in further decrease in compactibility. Milling counteracts the effect of wet granulation on MCC compactibility as particle surface area and porosity are increased by milling.