Study of the Pseudo-Crystalline Transformation from Form I to Form II of Thiamine Hydrochloride (Vitamin B1)

Abstract

There are three types of pseudo-polycrystalline forms of thiamine hydrochloride (vitamin B 1 ): form I (monohydrate); form II (hemihydrate); and form III (anhydrate). These crystal structures were elucidated using single-crystal X-ray structural analysis, form I by Kraut and Reed in 1962, 1) form II by Watanabe et al. in 1979, 2) and form III by Te et al. in 2003. 3) Since then, there have been various reports on the physiochemical properties of these pseudo-polycrystalline forms. 4,5) The relationship between form I (monohydrate) and form III (anhydrate) is that of the enantiotropic transformation accompanying changes in the hydration state. The pseudo-crystalline transformation from form I to form III is achieved by drying, and form III returns to form I by rehydration. The reversibility of form I and form III as well as the dehydration behavior of form II were reported in detail based on each crystal structure. 6,7) It was reported that the pseudo-crystalline transformation from form I to form II occurs when form I is stored for a long time under usual laboratory conditions, in a wet granulation process, in a slurry wash with water, or under specific conditions of 40°C and 75% relative humidity (RH). 2,8) However, the elucidation of the rate of the pseudo-crystalline transformation depending on storage conditions was lacking. The present study was therefore undertaken to examine the pseudo-crystalline transformation behavior from form I to form II in detail, including kinetic analysis by varying the storage conditions of temperature and humidity. In addition, we aimed to determine whether the rate was affected by formulation with establishing the most appropriate method to detect small amounts of the crystalline polymorph in tablets.As part of the evaluation of the quality of tablets, which are the final product, the evaluation of crystalline forms of drug substances is important in the quality control of pharmaceutical products. Even if the crystalline form of drug substances in a tablet changes, it is not easy to confirm small amounts of crystalline change in drug substances when combined with various excipients. In this study, we observed changes in the crystalline forms of thiamine hydrochloride in tablets using the synchrotron X-ray powder diffraction (XRPD) method which allows sensitive measurement with parallel bright X-ray beams. We have optimized the methodology of synchrotron XRPD to detect small amount of the drug substance. The detection rate using this methodology is equivalent to about 0.02% of the amount of drug substances in a common size tablet. The details of this methodology will be published separately in the near future. In addition to the high sensitivity, it should be emphasized that the XRPD method is a non-destructive inspection, and the whole tablets can be used as specimen without grinding preparation by utilizing the advantage of highly brilliant and parallel synchrotron radiation. ExperimentalMaterials Form I thiamine hydrochloride crystals were purchased from Sigma Chemical (...

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