Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, Punjab, India.
Eur J Pharm Sci. 2011 Sep 18;44(1-2):136-41. doi: 10.1016/j.ejps.2011.06.018. Epub 2011 Jul 13.
This manuscript studies the effect of counterion on the phase behaviour during lyophilization of indomethacin salts. Salt forms of indomethacin namely, sodium, potassium, rubidium and cesium were prepared in situ and analyzed by modulated differential scanning calorimetry (MDSC) for determination of the critical process parameter for lyophilization. At a cooling rate of 17°C/min, indomethacin salts separated as amorphous form on freeze concentration. Tg' of indomethacin salts followed the order: sodium (-35.36°C)>potassium (-38.90°C)>rubidium (-43.70°C)>cesium (-47.84°C) salt. Tg' was followed by crystallization exotherm during the heating run for all salts, except indomethacin cesium. At slower cooling rates (0.5 and 1°C/min), indomethacin sodium, potassium and rubidium crystallized in the cooling run, while indomethacin cesium remained amorphous. The differential crystallization behaviour of indomethacin salts was explained in terms of bulkiness of the counterion, molecular interactions and structural relaxation behaviour near Tg'. The research work has implications in lyophilization processing as well as the stability and performance of final product.
本文研究了共离子对吲哚美辛盐冷冻干燥过程中相行为的影响。通过调制差示扫描量热法（MDSC）原位制备了吲哚美辛的钠盐、钾盐、铷盐和铯盐，并分析其冷冻干燥的关键工艺参数。在 17°C/min 的冷却速率下，吲哚美辛盐在冷冻浓缩时分离为无定形形式。吲哚美辛盐的 Tg'顺序为：钠（-35.36°C）>钾（-38.90°C）>铷（-43.70°C）>铯（-47.84°C）盐。除了吲哚美辛铯盐之外，所有盐在加热过程中都遵循 Tg'之后的结晶放热顺序。在较慢的冷却速率（0.5 和 1°C/min）下，吲哚美辛的钠盐、钾盐和铷盐在冷却过程中结晶，而吲哚美辛的铯盐仍保持无定形状态。根据共离子的体积、分子相互作用和 Tg'附近的结构弛豫行为，解释了吲哚美辛盐的差示结晶行为。这项研究工作对冷冻干燥过程以及最终产品的稳定性和性能都有影响。
