Effect of Several Cellulosic Binders and Method of Their Addition on the Properties and Binder Distribution of Granules Prepared in an Agitating Fluidized Bed.

Abstract

A model system consisting of lactose-cornstarch was used to examine the effect of five cellulosic binders [hydroxypropylcellulose (HPC)(6cP), hydroxypropylmethylcellulose 2910 (HPMC)(3, 6, 15cP) and methylcellulose (MC)(15cP)] on the particle size distribution of granules prepared in an agitating fluidized bed under fixed operating conditions. The distribution of binder in different size fractions of granules was also determined by measuring the contents of methoxyl and hydroxypropoxyl groups. When the binders were added by the solution method, higher solution viscosity resulted in the granule size being increased, with almost equivalent binder distributions in different size fractions. The granules prepared by the dry mixing method with HPC (6cP) or HPMC (3cP) also showed a good correlation between median particle size and binder level, though the binders were concentrated in the coarse-sized particle fractions of the granules. The results are consistent with our previous findings on wet granulation with a fluidized bed. When a trace amount of water-soluble dye was mixed with the granulating liquid or powder components to examine the granulation mechanism in both the solution and the dry mixing methods of binder addition, the dye distributions were more uniform than the binder distributions, especially in the dry mixing method. This suggests that the solubility of binders or dye in water is a critical factor determining their distribution in the different size fractions of the granules.