Investigation on agglomeration kinetics of acetaminophen using fluidized bed wet granulation

Abstract

Acetaminophen is a well-known medicine frequently used as analgesic in fever treatment. In pharmaceutical formulation procedure, batch fluidized bed wet granulation is a bottleneck process for the continuous processing of acetaminophen from powder to solid dosage form. To meet the market demand and reduce operating costs, fluid bed wet granulation needs process intensification by converting batch to continuous process. For the scale-up and batch to continuous conversion procedure, investigation on acetaminophen agglomeration kinetics is necessary. Therefore, this work investigates agglomeration kinetics of acetaminophen through batch fluidized bed wet granulation experiments, and the kinetic parameters are estimated using inverse modeling. Experiments are conducted on a 5-L capacity pilot scale batch fluidized bed granulator. The effects of various process parameters, namely, binder concentration, spray rate, atomization pressure, and batch size, on particle size distribution are investigated. A 1-D population balance model with Equi-Kinetic Energy kernel for agglomeration is simulated to compare with the experimental data. The mean particle diameter increased when binder spray rate and binder concentration are increased and that the mean particle diameter decreased with increase in the atomization pressure and batch size. Experiments data comparison with the model can be used for process intensification with reasonable accuracy.