Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Pharm Sci. 2010 Sep;99(9):3941-52. doi: 10.1002/jps.22240.
Thiamine hydrochloride (THCl) can exist as an anhydrate (AH), a hemihydrate (HH) and as a nonstoichiometric hydrate (NSH) where the water content can range between 0 and approximately 1 mole of water per mole of THCl. We have investigated the NSH --> HH phase transformation, in the presence of microcrystalline cellulose (MCC), following (i) wet massing, (ii) fluid-bed granulation, and (iii) exposure to water vapor (40 degrees C/75% RH). Based on Raman spectroscopy (40 degrees C), wet massing of NSH alone caused near complete transformation to HH in <100 min. In the presence of MCC, the transformation rate was decelerated. During fluid-bed granulation, approximately 20% of NSH was transformed to HH and the deceleratory effect of MCC was much less pronounced. Exposure to water vapor, of both NSH-MCC powder blends and granules (prepared by fluid-bed) resulted in complete HH formation within 6 days. Presence of MCC in the powder blend did not affect HH formation kinetics, but facilitated phase transformation in the granules. NSH --> HH conversion appeared to follow two-dimensional nucleation and growth model in powder blends, whereas the granules showed either three-dimensional diffusion controlled or a first-order kinetics. In a wet mass, polyvinyl pyrrolidone, a widely used binder, was much more effective than MCC in inhibiting HH formation during wet massing.
盐酸硫胺素（THCl）可以以无水物（AH）、半水合物（HH）和非化学计量水合物（NSH）的形式存在，其中含水量可以在 0 到大约 1 摩尔水/摩尔 THCl 之间变化。我们研究了在微晶纤维素（MCC）存在下的 NSH---> HH 相转变，包括（i）湿混，（ii）流化床造粒，和（iii）暴露在水蒸气中（40°C/75%RH）。基于拉曼光谱（40°C），单独的 NSH 湿混在<100 分钟内几乎完全转化为 HH。在 MCC 的存在下，转化速率被减缓。在流化床造粒过程中，大约 20%的 NSH 转化为 HH，而 MCC 的减速效果不那么明显。暴露在水蒸气中，无论是 NSH-MCC 粉末混合物还是颗粒（通过流化床制备），在 6 天内都完全形成了 HH。MCC 存在于粉末混合物中并不影响 HH 形成动力学，但促进了颗粒中的相转变。NSH---> HH 的转化似乎在粉末混合物中遵循二维成核和生长模型，而颗粒则表现出三维扩散控制或一级动力学。在湿混中，聚维酮（一种广泛使用的粘合剂）比 MCC 更有效地抑制 HH 的形成。
