Mistry Pinal, Chakravarty Paroma, Lubach Joseph W
Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota, 55414, USA.
Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, Mailstop 432a, South San Francisco, California, 94080, USA.
Pharm Res. 2016 Oct;33(10):2470-80. doi: 10.1007/s11095-016-1972-7. Epub 2016 Jun 20.
To characterize the distribution of water among various components in a powder blend using solid-state NMR spectroscopy.
Water sorption behavior of theophylline anhydrate and excipients was determined by dynamic vapor sorption (DVS) and Karl Fischer Titration (KFT) after storing them in humidity chambers for 1 week at room temperature (RT) and calibration curves were generated for water content vs. (1)H T 1 relaxation times. Powder blends (either with microcrystalline cellulose or lactose as diluent) were stored at different relative humidity (RH) conditions and analyzed periodically using solid-state NMR, powder X-ray diffraction, and KFT.
Anhydrous theophylline converted to the hydrate at ≥ 84% RH. Based on the calibration curves of water content vs. relaxation times, the distribution of water in the powder blends was estimated. The total water content calculated using ssNMR was in good agreement with values measured using KFT. In blends stored at 90% RH, theophylline anhydrate-to-hydrate conversion did not occur in 1 week.
The distribution of water in multi-component powder blends was successfully determined using correlation between (1)H T 1 relaxation times and total water content. Excipient water sorption inhibited hydrate formation in theophylline at 90% RH. Water distribution was affected by excipient type. The extent of water sorbed by excipients in blends was found to be different than their standalone equilibrium water content.
使用固态核磁共振光谱法表征粉末混合物中各组分间水的分布情况。
将无水茶碱和辅料在室温下于湿度箱中储存1周后，通过动态蒸汽吸附（DVS）和卡尔费休滴定法（KFT）测定其水吸附行为，并生成水含量与（1）H T1弛豫时间的校准曲线。粉末混合物（以微晶纤维素或乳糖作为稀释剂）在不同相对湿度（RH）条件下储存，并定期使用固态核磁共振、粉末X射线衍射和KFT进行分析。
无水茶碱在相对湿度≥84%时转化为水合物。根据水含量与弛豫时间的校准曲线，估算了粉末混合物中水的分布。使用固态核磁共振计算的总水含量与使用KFT测量的值高度吻合。在90%相对湿度下储存的混合物中，无水茶碱在1周内未发生向水合物的转化。
利用（1）H T1弛豫时间与总水含量之间的相关性，成功测定了多组分粉末混合物中水的分布。辅料的水吸附在90%相对湿度下抑制了茶碱中水合物的形成。水的分布受辅料类型影响。发现混合物中辅料吸附的水量与其单独的平衡水含量不同。
