DSC. Thermal analytical data of 3–5 mg of solids placed in perforated, aluminum-sealed 60-µL pans were collected on a calorimeter (DSC-7, Perkin Elmer Instruments, Shelton, CT) with a temperature-scanning rate of 10 °C/min from 50 to 200 °C for carbamazepine 5 °C/min from 50 to 170 °C for cimetidine (mainly for the crystallinity measurements), and 8 °C/min from 50 to 130 °C for phenylbutazone using nitrogen 99.990% as a blanket gas (36, 43, 57, 62). The temperature axis was calibrated with indium 99.999 % (Perkin Elmer Instruments) with a melting onset at 156.6 °C. DSC provided the thermodynamic relationship between different polymorphs (i.e., forms) and information about crystallinity and the melting point of the API solids. The percent of crystallinity was calculated by dividing the area of a sample melting peak by the largest melting peak area of all samples.

TGA. TGA analysis was carried out by TGA heating balance (TGA 7, Perkin Elmer Instruments) to monitor sample weight loss as a function of temperature. The heating rate was 10 °C/min from 50 to 200 °C, 5 °C/min from 50 to 170 °C, and 8 °C/min from 50 to 130°C for carbamazepine, cimetidine, and phenylbutazone, respectively (36, 43, 57, 62). Weight loss was usually associated with either solvent evaporation close to the boiling point of a solvent, as in the case of solvates, or sample decomposition. The open platinum pan and stirrup were rinsed by ethanol and burned by a spirit lamp to remove all impurities. All samples were heated under nitrogen atmosphere to avoid oxidization. About 3 mg of sample were placed on the open platinum pan suspended in a heating furnace.

Transmission FTIR spectroscopy. Transmission FTIR spectroscopy was used to measure purity, detect bond formation, and verify chemical identity. Transmission FTIR spectra were recorded on a spectrometer (Spectrum One, Perkin Elmer Instruments). Approximately 1 mg of sample was ground gently with 99 mg of 50 °C oven-dried KBr in an agate mortar and pestle to avoid polymorphic transition induced by extended grinding. The round KBr sample disk was prepared by a uniaxial press with a pressure of 7 tons. The disk was scanned with a scan number of 8 from 450 to 4000 cm^-1, with a resolution of 2 cm^-1.

This work was supported by a grant from the National Science Council of Taiwan (NSC 95-2113-M-008-012-MY2). Suggestions from Jui-Mei Huang, of the Precision Instrument Center in National Central University, about DSC and from Ching-Tien Lin, also of the Precision Instrument Center in National Central University, about SEM are gratefully acknowledged.

Tu Lee* is an associate professor, and Yan Chan Su, Hung Ju Hou, and Hsiang Yu Hsieh are graduate students, all at National Central University, 300 Jhong-Da Rd., Jhong-Li City 320, Taiwan, ROC, tel. +886 3 422 7151 ext. 34204, fax 886 3 425 2296, tulee@cc.ncu.edu.tw

*To whom all correspondence should be addressed.

Submitted: July 8, 2008. Accepted: Sept. 15, 2008.

Note
The results and related discussion will be included in Part 2 of this article, which will appear in the June issue of Pharmaceutical Technology.