Effect of counterion on the phase behaviour during lyophilization of indomethacin salt forms.

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.