WET-GRANULATION RESEARCH WITH APPLICATION TO SCALE-UP

摘要

Granulation is a unit operation by which larger granules are produced from fine, powdery particles to improve appearance, flow properties and mixedness, reduce dustiness and, in general, produce engineered particles with superior attributes. Agglomeration in wet granulation is achieved by introducing a "binder" fluid onto a shearing mass of fine powders. This paper gives a general overview of the process with emphasis on a simplified granulation model based on a dimensionless parameter containing inertia and viscous dissipation energies between colliding particles: the so-called Stokes number. The model incorporates most common features of all granulation devices (mixers) used in the pharmaceutical industry. Also described in the paper is a computer simulation that captures the movement of flowing powder in an ideal mixer-granulator with constant shear rate. A fraction of the total number of particles is wet (covered by binder and therefore "sticky") while the rest of the particles are dry. The numerical simulation depicts two distinct regimes of agglomeration found in a typical granulator: granule growth and subsequent breakup. During granule growth-simulations, final granule size and shape distributions are obtained by analyzing the size and shape of formed granules using a pattern-recognition technique. A second kind of simulation, also using rapid granular flow modeling, follows the rotation and deformation of an "agglomerate" held together by a liquid binder. Results from these simulations yield critical values of the Stokes number. Below the critical value, the agglomerates are stable and only rotate in response to shear while above the critical value they break into two or more pieces. At the critical value, they attain a steady elongated shape. Using values of the critical Stokes number, the model predicts the size of formed granules. The existence of the critical state in which granules attain a characteristic elongated shape is used to measure shear forces in a granulator by employing calibrated "test" particles of known strength. This knowledge is employed in granulation scale-up to determine a kinematic rule that conserves stresses in the small and the large-scale machines. It was found that conserving the magnitude of internal stresses in the moving powder yields granules with similar attributes in granulators of different size.