Granulations in a Fluidized-Bed: Effect of Binders and Their Concentrations on Granule Growth and Modeling the Relationship Between Granule Size and Binder Concentration

Abstract

Lactose and mixture of lactose and microcrystalline cellulose (1:1) were granulated in a fluid-bed equipment using PVP, acacia and gelatin as binders. The effect of these binders, their concentrations, and volume of granulation liquid on granule growth and granule sue distribution was studied. It has been shown that individual binder and binder concentration affect granule growth and growth mechanism. Also, the volume of granulation liquid and part dissolution of excipients being granulated contribute significantly to the granule size and size distribution. On the basis of granule growth data, a mathematical relationship which relates granule size as a function of binder concentration is proposed. Granule growth constant for the binders is computed from the granule size against binder concentration data. The constant describes granule growth pattern, and is termed as binder coefficient, β. The numerical value of binder coefficient, which varies with the binder, indicates relative activity and effectiveness of each individual binder. A relationship between the binder coefficients is also established. This is shown to predict granule sue for a binder relative to another binder for the desired concentration. The validity and the applicability of the proposed relationship was tested on the data obtained during present investigations as well as on data reported by other authors.