Practical Approach for Measuring Heat Capacity of Pharmaceutical Crystals/Glasses by Modulated-Temperature Differential Scanning Calorimetry

• Published in: Chemical & pharmaceutical bulletin Vol. 61; no. 3; pp. 315 - 319
• Main Authors: Harada, Takuji, Kawakami, Kohsaku, Yoshihashi, Yasuo, Yonemochi, Etsuo, Terada, Katsuhide, Moriyama, Hiroshi
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.03.2013; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Acetaminophen - chemistry; amorphous; beta-Cyclodextrins - chemistry; Calorimetry, Differential Scanning - methods; crystal; Crystallization - methods; differential scanning calorimetry; Gases - chemistry; heat capacity; Hot Temperature; Indomethacin - chemistry; Powders - chemistry; Reproducibility of Results; Temperature
• ISSN: 0009-2363; 1347-5223
• 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.