Influence of granulating method on physical and mechanical properties, compression behavior, and compactibility of lactose and microcrystalline cellulose granules

The physical and mechanical properties of lactose (LC) and microcrystalline cellulose (MCC) granules prepared by various granulating methods were dete rmined, and their effects on the compression and strength of the tablets we re examined. From the force-displacement curve obtained in a crushing test on a single granule, all LC granules appeared brittle, and MCC granules wer e somewhat plastically deformable. Intergranular porosity epsilon(inter) cl early decreased with greater spherical granule shape for both materials. De crease in intragranular porosity epsilon(intra) enhanced the crushing force of a single granule F-g. Agitating granulation brought about the most comp actness and hardness of granules. In granule compression tests, the initial slope of Heckel plots K-1 appeared closely related to ease of filling void s in a granule bed by the slippage or rolling of granules. The reciprocal o f the slope in the succeeding step 1/K-2 in compression of MCC granules ind icated positive correlation to F-g, while in LC granules, no such obvious r elation was evident. 1/K-2 differed only slightly among granulating methods . Tensile strength of tablets T-1 obtained by compression of various LC gra nules was low as a whole and was little influenced by granulating method. F or MCC granules, which are plastically deformable, tablet strength greatly depended on granulation. Granules prepared by extruding or dry granulation gave strong tablets. Tablets prepared from granules made by the agitating m ethod showed particularly low T-1. From stereomicroscopic observations, the contact area between granule particles ina tablet appeared smaller; this w ould explain the decrease in intergranular bond formation.