酮洛芬对映体在Chiralpak AD上具有连续温度相关参数的竞争吸附平衡模型

Competitive Adsorption Equilibrium Model With Continuous Temperature Dependent Parameters for Ketoprofen Enantiomers on Chiralpak AD Column

结晶原理和色谱原理是拆分手性药物用到的两大主要原理,而高效液相色谱法和模拟移动床(SMB)色谱分离技术是利用色谱原理拆分手性药物的两大重要手段。本研究用高效液相色谱法测定了酮洛芬对映体在Chiralpak AD柱中,以正己烷和乙醇(体积比80∶20)为流动相,多温度下的流出曲线。并以此为基础用拟合度最好的八参数bi-Langmuir模型,运用逆向法来考察该药物对映体在不同温度下,温度对竞争吸附等温线参数的影响,并对3温度下的酮洛芬过载曲线同时拟合,确定出bi-Langmuir中受温度影响的模型参数。

Competitive adsorption equilibrium of ketoprofen enantiomers on Chiralpak-AD column with n-hexane and ethanol(80∶20) as the mobile phase was acquired using inverse method. Conventional transport-disperse(TD) model was used to describe materials balances in the chromatography column. TD model parameters were estimated based on linear pulse responses measured at different flowrates. Overloaded band profiles were then measured at three different temperatures. Parameters of temperature dependent bi-Langmuir model were obtained by fitting the experimentally measured band profiles. Three additional parameters for adsorption heat were used to give binary equilibrium correlation with continues temperature dependence. The determined parameters were further verified by comparing model predictions with band profiles that were independently measured and not used in the data fitting process.