Kinetics Estimation and Polymorphic Transformation Modeling of Buspirone Hydrochloride

• 作者: Mehdi Sheikhzadeh Milana Trifkovic Sohrab Rohani
• 来源期刊: 结晶过程及技术期刊(英文)
• 学科: 医学
• 关键词: BUSPIRONE HYDROCHLORIDE POLYMORPH TRANSFORMATION RAMAN Spectroscopy KINETICS of TRANSFORMATION
• 年，卷（期）: 2012,（2）
• 页码范围: 31-43
• 页数: 13页
• 分类号: R73

摘要

In this work, solvent-mediated polymorphic transformation of metastable Form II to stable Form I of Buspirone Hy-drochloride (BUS-HCl) was studied. The polymorphic transformation was monitored using in-situ Raman spectroscopy. The solvent-mediated transformation process is governed by the dissolution of Form II and the nucleation and subsequent growth of Form I. The model parameters for each of these sub-processes were determined with the aid of experimental data including polymorphic fraction in solid phase, solute concentration, and the crystal size distribution. In order to estimate the kinetic parameters, independent seeded batch sets of experiments were conducted, first to estimate the growth rate of Form I, and consequently to estimate the secondary nucleation of Form I and dissolution rate of Form II. The experimental data showed that the secondary nucleation of Form I occurred slightly after the dissolution of Form II was initiated. The estimated parameters for growth, nucleation and dissolution rates were successfully implemented in the population model and validated with the experiments.