The effect of the physicochemical properties of an aqueous hydroxypropylcellulose (HPC) binder solution and different pharmaceutical excipients on the agglomeration kinetics and granule properties was investigated for combinations of common pharmaceutical excipients. Pure component and two-component blends of microcrystalline cellulose, lactose monohydrate, dicalcium phosphate and mannitol were granulated in a pilot plant Wurster granulator using a 15% HPC solution. Experimental conditions and solution concentration were chosen based on knowledge gained through a previous investigation of this agglomeration process [1]. The current work extends the previous study by encompassing a wider range of pharmaceutically relevant excipient combinations and with additional granule characterization beyond the scope of previous work. Granule growth kinetics were found to vary widely for the different blends. The properties of granules produced in pure component experiments correlated well with and were predictive of granule properties of the blends. The mechanical properties of compressed tablets, as measured in compaction simulation experiments, were inversely related to the granule growth rate. Attrition testing was also employed to determine the strength of granule blends. Physically-based criteria [2] were evaluated, which use the morphological properties of these excipients (size and surface roughness) together with physical properties of the binder solution for prediction of the coating vs. agglomeration regime at given flow conditions (collision velocity). This criteria based simulation was effective at the relative growth rates of blends.

[1] Rajniak, P., Mancinelli, C., Chern, R.T., Stepanek, F., Farber, L., Hill, B.T., Experimental study of wet granulation in fluidized bed: Impact of the binder properties on the granule morphology, International Journal of Pharmaceutics (2006), 334 (2007) 92-102.

[2] Ennis, B.J., Tardos, G.I., Pfeffer, R., 1991. A microlevel-based characterization of granulation phenomena. Powder Technol. 65, 257-272.