Ariyasu Aoi, Hattori Yusuke, Otsuka Makoto
Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishi-Tokyo, Tokyo, 202-8585, Japan.
Research Institute of Pharmaceutical Sciences, Musashino University, 1-1-20 Shinmachi, Nishi-Tokyo, Tokyo, 202-8585, Japan.
Int J Pharm. 2017 Jun 15;525(1):282-290. doi: 10.1016/j.ijpharm.2017.04.017. Epub 2017 Apr 8.
The coating layer thickness of enteric-coated tablets is a key factor that determines the drug dissolution rate from the tablet. Near-infrared spectroscopy (NIRS) enables non-destructive and quick measurement of the coating layer thickness, and thus allows the investigation of the relation between enteric coating layer thickness and drug dissolution rate. Two marketed products of aspirin enteric-coated tablets were used in this study, and the correlation between the predicted coating layer thickness and the obtained drug dissolution rate was investigated. Our results showed correlation for one product; the drug dissolution rate decreased with the increase in enteric coating layer thickness, whereas, there was no correlation for the other product. Additional examination of the distribution of coating layer thickness by X-ray computed tomography (CT) showed homogenous distribution of coating layer thickness for the former product, whereas the latter product exhibited heterogeneous distribution within the tablet, as well as inconsistent trend in the thickness distribution between the tablets. It was suggested that this heterogeneity and inconsistent trend in layer thickness distribution contributed to the absence of correlation between the layer thickness of the face and side regions of the tablets, which resulted in the loss of correlation between the coating layer thickness and drug dissolution rate. Therefore, the predictability of drug dissolution rate from enteric-coated tablets depended on the homogeneity of the coating layer thickness. In addition, the importance of micro analysis, X-ray CT in this study, was suggested even if the macro analysis, NIRS in this study, are finally applied for the measurement.
肠溶衣片的包衣层厚度是决定药物从片剂中溶出速率的关键因素。近红外光谱法（NIRS）能够对包衣层厚度进行无损快速测量，从而可以研究肠溶衣层厚度与药物溶出速率之间的关系。本研究使用了两种市售的阿司匹林肠溶片产品，研究了预测的包衣层厚度与获得的药物溶出速率之间的相关性。我们的结果显示其中一种产品存在相关性；药物溶出速率随肠溶衣层厚度的增加而降低，而另一种产品则不存在相关性。通过X射线计算机断层扫描（CT）对包衣层厚度分布进行的进一步检查显示，前一种产品的包衣层厚度分布均匀，而后一种产品在片剂内部表现出不均匀分布，并且片剂之间的厚度分布趋势也不一致。有人认为，这种厚度分布的不均匀性和不一致趋势导致片剂正面和侧面区域的层厚度之间缺乏相关性，从而导致包衣层厚度与药物溶出速率之间失去相关性。因此，肠溶衣片药物溶出速率的可预测性取决于包衣层厚度的均匀性。此外，本研究表明，即使最终应用宏观分析方法（本研究中的近红外光谱法）进行测量，微观分析方法（本研究中的X射线CT）也很重要。
