The characterization and comparison of spray-dried mannitol samples.

BACKGROUND: Following the production of spray-dried mannitol powders, it is essential that the polymorphic content of each individual product is completely characterized. The implications of the polymorphic behavior of mannitol are immense. The appearance or disappearance of a crystalline form within a dosage form can have costly repercussions and lead to a dosage form being withdrawn.

METHOD: In this study, commercially available and laboratory-produced spray-dried mannitol products were characterized to establish the polymorphic content of each. Their polymorphic behavior was also characterized after laboratory scale pharmaceutical processes. Thermal analysis employed differential scanning calorimetry, thermogravimetric analysis, and isothermal microcalorimetry. Structural analysis of the samples was obtained using X-ray powder diffraction and Fourier transform Raman spectroscopy.

RESULTS: Structural analysis revealed that alpha- and beta- polymorphic forms were present in the commercial samples and some contained a mixture of polymorphs. Reprocessing employing spray drying indicated alpha- to beta- polymorphic transitions occurred within some of the samples.

CONCLUSION: It is essential that preformulation studies where spray-dried mannitol products are to be employed must take into account its polymorphic behavior upon supply, processing, and subsequent storage.