Strength and morphology of solid bridges in dry granules of pharmaceutical powders

Lactose granules prepared with pure ethanol are very weak, with crush strength comparable to that predicted by JKR theory, consistent with its negligible solubility. Mannitol, which is sparingly soluble, forms granules with bridge strength similar to the theoretical (Griffith) strength of a pure mannitol. Addition of HPC or PVP to the granulating solution produces bridges with strength comparable to that of pure polymer films. In comparison, the behavior of granules prepared with aqueous granulating solutions was much more complex due to the high saturation concentration of base powder. Granules produced with pure water had bridge strength approximately 20% of the theoretical strength. Addition of HPC or PVP to lactose granules increased the bridge strength modestly, but the strength was much smaller than that of the corresponding pure polymer films. Addition of HPC to mannitol granules had little effect on bridge strength, while PVP reduced bridge strength by approximately 30%. Addition of surfactants to the granulating solution also reduced dry bridge strength. These results reflect the complex microstructure and resulting mechanical properties of dry bridges produced by coprecipitation of the sugars and polymers (or surfactants).