Effect of Process Variables on the Properties and Binder Distribution of Granules Prepared by a High-Speed Mixer.

Abstract

A model system consisting of lactose-cornstarch-microcrystalline cellulose with hydroxypropyl methylcellulose 2910 (HPMC 3cP) as a binder was used to estimate the effects of process variables (granulation time, amount of granulating water and impeller speed) on the particle size distribution of granules prepared in a high-speed mixer using a dry mixing method of binder addition. The distribution of binder in different size fractions of granules was also determined by measuring the contents of methoxyl group. The binder content interpolated at the median particle size was close to the theoretical value calculated from the formulation. Longer granulation time, greater amount of granulating water and higher impeller speed increased the granule size and strength. An expanded binder distribution was seen at higher impeller speed. At extremely short granulation time (1 mins), the granules were friable and the binder content in the larger size fraction of the granules changed during fluid-bed and tray drying because of insufficient binder dissolution or granular compaction. Binder behavior during wet granulation seems to be closely related to the observed differences in granule strength.