The improved compaction properties of mannitol after a moisture-induced polymorphic transition.

We have previously shown that by exposing one form of mannitol to high relative humidity, a moisture-induced polymorphic transition of mannitol with a concurrent change in particle morphology occurs [Int. J. Pharm. 247 (2002) 69]. In this paper, we propose that if these changes occur during a wet-granulation procedure, it may be possible to make bring about an in situ size-reduction of mannitol with compaction property enhancement. Powder X-ray diffraction and scanning electron microscopy confirmed that a polymorphic transition (the delta form forming the beta form) had occurred on wet-granulation, and that a concomitant morphology change resulted in an agglomerate consisting of filament-like fine primary crystals (delta-granule). The aim of present study was to evaluate the compression properties of this agglomerate. The compact compressed with delta-granules possessed a tensile strength 1.5 times higher than other mannitol samples. Heckel analysis indicated that the mannitol compression process proceeded by deformation without fragmentation and was thus particle size dependent. The delta-granule showed enhanced plastic deformability, due to its unique particle structure. Because the intrinsic compression properties of the polymorphs were similar, the primary particle size and specific surface area of mannitol were indicated to be the major contributing factors for the improved compaction behaviour, rather than the polymorphic transition. When using the delta-granule as an excipient for a tablet formulation containing a high amount of phenylpropanolamine hydrochloride (PPA) as a poorly compactable model drug, excellent tablets could be prepared without capping, whereas conventional mannitol produced capped tablets.