Preparation of prolonged-release matrix tablet of acetaminophen with pulverized low-substituted hydroxypropylcellulose via wet granulation

Abstract

Pulverized L-HPC (low-substituted hydroxypropylcellulose, LH41) can be used as a prolonged-release matrix filler. LH41 powders with or without acetaminophen were granulated with ethanol or water to improve their micromeritic properties for practical tabletting by using a high-speed agitator, centrifugal fluidizing granulator or spray dryer. The water-granulated LH41 tablet was readily crushed under mechanical stress and rapidly disintegrated in water, resulting in rapid drug release. The ethanol-granulated LH41 provided a mechanically strong matrix tablet in which the drug was dispersed uniformly, resulting in prolonged drug release in water without disintegration. LH41 granules became swellable due to a physical crosslinking structure formed during granulation. The crosslinking structure in the ethanol-granulated LH41 was broken up during tablet preparation, with loss of the swelling properties. On the other hand, the LH41 granules prepared with water were mechanically strong, so that the physical crosslinking structure was retained in the tablet; consequently the tablet rapidly swelled and disintegrated.