Impact of non-binder ingredients and molecular weight of polymer binders on heat assisted twin screw dry granulation.

Two grades of commercial AFFINISOL™ HPMC HME were used as polymer binders to explore the influence of polymer viscosity and concentration on a novel heat assisted dry granulation process with a twin screw extruder. Contributions of other non-binder ingredients in the formulations were also studied for lactose, microcrystalline cellulose and an active pharmaceutical ingredient of caffeine. As sensitive indicators of processing conditions that expose the drug to high internally generated heat, dehydration of α-lactose monohydrate and polymorphic transformation of caffeine were monitored by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). Additionally, any decomposition of caffeine was determined by high-performance liquid chromatography (HPLC). Granular samples were characterized by particle size, circularity, fracture strength and their temperature on the exit of extruder. Higher screw speed and lower feed rate were found to help particles agglomerate by allowing feed particles a greater opportunity to increase in temperature. Lower binder molecular weight and higher binder concentration enable granules to build stronger strength and thereby lead to higher particle size. This new twin screw dry granulation was demonstrated as offering advantages over conventional hot melt granulation by minimizing thermal degradation of the tested ingredients.