Polymorphic changes of thiamine hydrochloride during granulation and tableting.

Thiamine hydrochloride was granulated using an instrumented fluidized bed granulator (Hüttlin HKC 05-TJ). Granules consisting of pure thiamine hydrochloride were produced using an aqueous solution of thiamine hydrochloride as the granulating liquid. The effects of process variables such as inlet air temperature, spray rate, and amount of granulating liquid on granule properties are described. Particle size distributions of granules depended mainly on the amount of granulating liquid sprayed into the powder bed. Granules were tableted on a rotary tablet press at four different compression forces. Crushing strengths and disintegration times of all tablets were found to be very low after manufacture, but increased considerably after 4 months of storage at room temperature. Granular materials showed "caking" under the same storage conditions. These changes could be attributed to alterations of the polymorphic form of thiamine hydrochloride. The water-free form, being present directly after granulation, absorbs humidity very fast and is transformed into the monohydrate, which is stable at room temperature. Loss of water takes place during the drying phase of the granulation process and on storage of the substance at temperatures of 50 degrees C and 80 degrees C. During storage at room temperature while exposed to humidity, a transformation into the hemihydrate was observed. This polymorph is transformed during thermal analysis at about 190 degrees C to a water-free form that is stable at higher temperatures.