Here, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process. Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone. The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered. The Stokes number was defined as the ratio of the inertial force to the viscous-damping force of a particle. We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters. Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface.Key words fluidized bed; granulation rate; mist diameter; contact angle; affinity; partial least squares regression Pharmaceutical industry uses granulation to add several functions to the original powder. For example, powder flowability can be improved by particle size enlargement, as the adhesion force is smaller than the gravity force for a coarse particle.1) Granulation can also be used to improve compactibility 2) and is effective for avoiding segregation.
1)Fluidized bed granulation is a popular granulation method used in several industries, as granulation and drying can be conducted in a single system, effectively avoiding contamination by foreign materials and expediting production.3) In fluidized bed granulation, raw powdered material is fluidized by heated air, followed by spraying binder solution to bind the powder. Because the particle size of a granule often affects the quality of the final product of the oral dosage form, it is important to understand which critical factors affect the granulation rate.Shaefer et al. 4) and Nishimura et al. 5) investigated the influence of mist diameter in the fluidized bed granulation process, noting a positive correlation in granule size and spray mist diameter. However, the Schaefer report also indicated that this relationship varies with the material used for binding, suggesting that other factors also contribute to the granulation rate.Watano et al. 6) considered the effects of moisture content on granulation rate, finding that moisture content has a significant effect on particle size-but only if the moisture content region exceeds 7% of the formulation. Two reports by Jaiyeoba and Spring 7,8) measured the contact angle of a water droplet for various excipients, finding that a lower contact angle correlates wit...
