Abstract
A model system consisting of lactose-cornstarch-microcrystalline cellulose was used to study the effect of five cellulosic binders [hydroxypropylcellulose (HPC) (6 cP), hydroxypropylmethylcellulose 2910 (HPMC) (3, 6, 15 cP), and methylcellulose (MC) (15 cp)] on particle size distribution of granules prepared by a high-speed mixer under fixed operating conditions. The distribution of binder in different size fractions of granules was 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 percentage of coarse particles generated in the granules being increased without an increase in the median particle size. The granules prepared by the dry mixing method with HPC (6 cP) or HPMC (3 cP) showed a good correlation between their median particle size and binder level. Other binders did not show such a correlation, as higher concentrations of the binders were present in smaller particle fractions of the granules with an increase in binder level. When binders were dissolved completely in the dry mixing method, a good correlation between median particle size and binder level was observed. The analysis of granule size dependency of binder content appeared to be useful for evaluating the effectiveness of binders in the dry mixing method.
