Development and Optimization of a Wet Granulation Process at Elevated Temperature for a Poorly Compactible Drug Using Twin Screw Extruder for Continuous Manufacturing.

The objective of this study was to enhance tabletability of a poorly compactible drug, acetaminophen, by wet granulation using twin screw extruder at high temperature. It was desired that there would be minimum amounts of excipients used and the granules obtained after extrusion would be dry and fall within a size range suitable for tableting without any further processing. Mixtures of acetaminophen (95%) with binders (5% povidone or partially pregelatinized starch) were wet granulated through twin screw extruder at 70°C by adding 7% w/w water. The process had a short granulation time (<1 min), and, on account of the elevated processing temperature used, no drying after extrusion was needed. By optimizing formulation and processing parameters, >90% granules in the size range of 125 to 1000 μm (<3% above 1000 μm and <7% below 125 μm) were obtained without any milling. When the granules were compressed by adding 1% disintegrant and 0.5% lubricant extragranularly, tablets produced (93.6% drug load) had good mechanical strength having hardness >1.7 MPa, which was superior to that of tablets prepared by conventional high shear wet granulation. As the granules could be extruded continuously and did not require drying and milling, the method was amenable to continuous processing.