화학공학소재연구정보센터
Journal of Chemical Engineering of Japan, Vol.50, No.7, 501-510, 2017
Development of a Circulated Flow Mixing Method with a Tubular Crystallizer for Controlling Indomethacin Polymorphs
A circulated flow mixing method with a tubular crystallizer was designed to separate the nucleation and crystal growth phases of pharmaceutical polymorphs for anti-solvent crystallization. The proposed method provides a fluctuating anti-solvent concentration due to the circulation of the active pharmaceutical ingredient (API) solution, whereas the anti-solvent concentration continually decreases in the simple addition method. The two methods were compared in the anti-solvent crystallization of indomethacin (IMC), a non-steroidal anti-inflammatory drug, in a water-acetone system at 50 degrees C. Furthermore, appropriate operating conditions that control the formation of two IMC polymorphs (i.e., a stable form gamma and an unstable form alpha) were investigated. The water addition rate was a key parameter controlling polymorph formation in both methods. Additionally, the proposed method provided a broader operation window to obtain the stable polymorph form gamma by controlling the water addition rate, which yielded a 20-fold higher productivity than the simple addition method.