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.

Laplace transform‐based approximation methods for solving pure aggregation and breakage equations

“…We have considered four test cases in this section that include binary breakage kernel: $$$ b\left(x,y\right)=\frac{2}{y} $$$ with $$$ S(x)=x,{x}^2 $$$ and Austin kernel: $$$ b\left(x,y\right)=\frac{3x}{y^2} $$$ with $$$ S(x)={x}^3 $$$ along with two initial conditions, that is, $$$ {u}_0(x)={e}^{-x},\delta \left(x-a\right) $$$. The applications of such physical parameters can be found in fluidized beds, the size distribution of raindrops and asteroids, and crushing/milling operations (see [3, 5] and further citations).…”

Effect of steel slag bed material on ash deposition and Na migration in circulating fluidised bed during Zhundong lignite combustion

“…17,20,27 In particular, the use of Mg-rich minerals being the bed material has been found effective in alleviating particle agglomeration, when magnesium presented at the outer layer of bed particles and prevented further reactions with alkali. 32,33 This indicates that similar applications may also go to the steel slag (SS), a by-product that enriches in Mg, Al and Si during steel production. 34 An annual SS production of 440 Mt by China's steel production industry is reported, 35 with a considerable proportion in the Xinjiang region but is merely regarded as a waste discarded in landfills or stockpiled.…”

“…These include but not limited to kaolin, Al 2 O 3 , sludge ash, phosphate rock and so forth and Mg‐bearing minerals and so forth 17,20,27 . In particular, the use of Mg‐rich minerals being the bed material has been found effective in alleviating particle agglomeration, when magnesium presented at the outer layer of bed particles and prevented further reactions with alkali 32,33 . This indicates that similar applications may also go to the steel slag (SS), a by‐product that enriches in Mg, Al and Si during steel production 34 .…”

Model-Based Scale-up Methodologies for Pharmaceutical Granulation

“…The granulation process is a commonly used process in the pharmaceutical industry. Through the granulation process, the shape and size of granules can be made large and uniform to increase the flowability and compressibility of powders [1,2]. Granulation processes are divided into wet granulation and dry granulation processes, depending on the use of binding solvent.…”