(748b) Experimental Measurement of the Cohesiveness of Fine Pharmaceutical Powders

Powder cohesion or cohesiveness (“stickiness”) remains a major challenge in the manufacture of pharmaceuticals. The phenomenon of cohesion relates to a number of practical industrial issues where particles interact under low load conditions (such as internal self-loading with minimal external loading from container) as well as playing a key role in controlling active powder flow where especially the tendency of some powders to agglomerate and offer poor flowability can be critical. This current work focuses on static particulate systems which relates directly to the behaviour of stored powders which includes the aerosolisation and entrainment of inhaled carrier/active particles ensembles.  In this study, a simple and robust test initially developed for soil mechanics, based on an unconfined compression test, was utilised to measure the powder cohesion of a number of commonly used pharmaceutical excipients (pre-gelatinised starch, dicalcium phosphate dehydrate, magnesium stearate, microcrystalline cellulose and a-lactose monohydrate), as well as number of surface treated excipients.  Cylinder shaped powder compacts of 1cm diameter and typically 1.5 cm high were prepared under low loads, and deformed using an unconstrained normal compression deformation for a series of common pharmaceutical excipients. Reproducible yield stresses were determined for all the powders tested, which are typified by the load versus displacement curves. Not only did the mechanical experiments give reliable and reproducible data, but this yield data was in turn correlated with the surface energy of the powders as determined using inverse gas chromatography.  This simple unconfined compression test was demonstrated to be capable of reliably measuring the cohesiveness of small amounts (1gm) of fine pharmaceutical powders. The determined yield stresses were found to correlate to the surface energy of the powders, including specifically D-mannitol powders which had their surface chemistry modified.