Formulation Development Department, Development & Planning Division, Nichi-Iko Pharmaceutical Co., Ltd.
Laboratory of Pharmaceutical Technology, School of Pharmacy and Pharmaceutical Sciences, University of Toyama.
Chem Pharm Bull (Tokyo). 2022;70(8):558-565. doi: 10.1248/cpb.c22-00261.
Hardness is a critical quality characteristic of pharmaceutical oral jelly. In this study, the hardness was determined by using the T relaxation curves measured by time-domain NMR. For sample preparation, kappa- and iota-carrageenans, and locust bean gum, were used as gel-forming agents. Ten test jellies with different gel-forming agent composition were prepared, and their hardness and T relaxation curves were measured by a texture analyzer and time-domain NMR (TD-NMR). A negative correlation between T relaxation time (T) and hardness was observed; however, it was difficult to determine the hardness directly from the T value. That is probably because the T relaxation curve contains information about molecular states, not only of water but also of the solute, and T values calculated by single-exponential curve fitting only express one property of the test jelly. By considering this issue, partial least squares (PLS) regression analysis was performed on the T relaxation curves for hardness determination of the test jellies. According to the analysis, an accurate and reliable PLS model was created that enabled accurate assessment of the hardness of the test jellies. TD-NMR enables the measurement of samples nondestructively and rapidly with low cost, and so could be a promising method for evaluation of the hardness of pharmaceutical oral jellies.
硬度是药物口服凝胶的一个关键质量特性。在本研究中，使用时域 NMR 测量的 T 弛豫曲线来确定硬度。对于样品制备，角叉菜胶和iota-角叉菜胶以及刺槐豆胶被用作凝胶形成剂。制备了具有不同凝胶形成剂组成的十种测试凝胶，并通过质构分析仪和时域 NMR（TD-NMR）测量其硬度和 T 弛豫曲线。观察到 T 弛豫时间（T）与硬度之间存在负相关；然而，很难直接从 T 值确定硬度。这可能是因为 T 弛豫曲线不仅包含水的分子状态信息，还包含溶质的分子状态信息，并且通过单指数曲线拟合计算出的 T 值仅表达测试凝胶的一种性质。考虑到这个问题，对 T 弛豫曲线进行了偏最小二乘（PLS）回归分析，以确定测试凝胶的硬度。根据分析，创建了一个准确可靠的 PLS 模型，能够准确评估测试凝胶的硬度。TD-NMR 能够以低成本快速无损地测量样品，因此可能是评估药物口服凝胶硬度的一种很有前途的方法。
