Harada Takuji, Kawakami Kohsaku, Yoshihashi Yasuo, Yonemochi Etsuo, Terada Katsuhide, Moriyama Hiroshi
Biomaterials Unit, International Center for Materials Nanoarchitectonics, National Institute for Materials Science, Tsukuba, Ibaraki, Japan.
Chem Pharm Bull (Tokyo). 2013;61(3):315-9. doi: 10.1248/cpb.c12-00928.
A practical protocol to obtain accurate heat capacity values of pharmaceutical compounds using modulated-temperature differential scanning calorimetry was established. Three pharmaceutical compounds, acetaminophen, indomethacin, and tri-O-methyl-β-cyclodextrin were used as model compounds. Powder samples did not produce reproducible results, presumably due to inclusion of gas in gap of powders that influenced the measured heat capacity and thermal homogeneity in the sample. Thus, the amorphous characteristics were evaluated using quench-cooled samples. Crystalline samples were obtained by partially melting the sample to allow recrystallization using the residual crystal as a template. Optimum sample mass was about 10 mg. Use of too small sample size resulted in poor reproducibility due to localization of the sample in the pan, while too large size resulted in low heat capacity values probably because of heterogeneity of the sample temperature. The optimum modulation period was in the range of 60 s and 90 s, to which the ramp rates of 2°C/min and 1°C/min, respectively, were applied. The ramp amplitude was less significant in the evaluation. This information should help in comprehending basic characteristics of pharmaceutical compounds.
建立了一种使用调制温度差示扫描量热法获得药物化合物准确热容值的实用方案。选用对乙酰氨基酚、吲哚美辛和三 - O - 甲基 - β - 环糊精三种药物化合物作为模型化合物。粉末样品无法产生可重复的结果，推测是由于粉末间隙中包含气体，影响了样品的测量热容和热均匀性。因此，使用骤冷样品评估非晶特性。通过将样品部分熔化，以残留晶体为模板使其重结晶来获得结晶样品。最佳样品质量约为10毫克。使用过小的样品量会因样品在样品盘中的局部化而导致重现性差，而过大的样品量可能由于样品温度不均匀导致热容值较低。最佳调制周期在60秒至90秒范围内，分别应用2°C/分钟和1°C/分钟的升温速率。升温幅度在评估中不太重要。这些信息有助于理解药物化合物的基本特性。
