Institute of Physics, Silesian University, ul. Uniwersytecka 4, 40-007 Katowice, Poland.
J Pharm Sci. 2010 Jan;99(1):94-106. doi: 10.1002/jps.21799.
Dielectric relaxation measurements as well as differential scanning calorimetry and X-ray diffraction investigations were performed on tramadol monohydrate and its hydrochloride salt. Examined samples do not crystallize during cooling and in consequence they reach the glassy state. In the case of the hydrochloride tramadol we are able to monitor alpha-relaxation process despite large contribution of dc conductivity to the loss spectra. It is the first such study on the salt of the drug. Up to now the dielectric spectroscopy has been regarded as useless in measuring such kind of API (active pharmaceutical ingredient). In this paper we also made some suggestions about the nature of the secondary relaxations in the amorphous tramadol monohydrate and its salt. The knowledge about the molecular mechanisms, which govern the observed secondary relaxations seems to be the key in predicting the stability of the amorphous form of the examined API. Finally additional dissolving measurements on the amorphous and crystal tramadol hydrochloride were performed. As a result we understood that dissolution properties of the amorphous form of the considered drug are comparable to those of crystalline one. However, we have found out that amorphous tramadol hydrochloride has greater ability to form tablets than its crystalline equivalent. This finding shows that amorphous drugs can be alternative even for the freely solved pharmaceuticals such as tramadol hydrochloride, because the former one has better ability to form tablets. It implies that during tabletting of the amorphous drugs there is no need to use any excipients and chemicals improving compaction properties of the API.
对曲马多一水合物及其盐酸盐进行了介电弛豫测量、差示扫描量热法和 X 射线衍射研究。研究样品在冷却过程中不会结晶，因此它们达到玻璃态。在盐酸曲马多的情况下，尽管直流电导率对损耗谱有很大贡献，我们仍能够监测到α弛豫过程。这是对该药物盐的首次此类研究。到目前为止，介电光谱学一直被认为在测量这种 API（活性药物成分）方面是无用的。在本文中，我们还对无定形曲马多一水合物及其盐的次级松弛的性质提出了一些建议。了解控制观察到的次级松弛的分子机制似乎是预测所研究 API 的无定形形式稳定性的关键。最后，对无定形和结晶盐酸曲马多进行了额外的溶解测量。结果表明，所考虑药物的无定形形式的溶解性质与结晶形式相当。然而，我们发现无定形盐酸曲马多比其结晶对应物具有更大的形成片剂的能力。这一发现表明，即使对于自由溶解的药物如盐酸曲马多，无定形药物也可以作为替代品，因为前者具有更好的形成片剂的能力。这意味着在无定形药物压片时，不需要使用任何赋形剂和改善 API 可压缩性的化学物质。
