Modelling,optimization And Experimental Study Of Aspirin Cooling Crystallisation Processes Based On Ultrasound

Particle size distribution is an important quality property which has major influence on the stability solubility and flowbility of the finial product in crystallization processes.Due to the advantage of real-time,no-invasive,automatic,facile,and reproducible measurements,ultrasonic technique as crystallization analysis is given more and more atttention,and developed quickly.The focus of the research reported in this thesis is placed on the computational and experimental study of Aspirin crystallization at process scale,investigationg the growth behavior of the population of crystals grown from a crystallizer.The constructed on-line measurement system of Aspirin cooling crystallization process by ultrasonic particle size analysis was applied to study the effect of cooling rate,stirring rate on particle size and shape distributions of product crystals as well as concentration.It was found that high cooling rate(1℃/min)and low stirring rate(100rpm)lead to large crystals of low aspect ratio.Low cooling rate(0.2℃/ min)results in slow growth.The case study crystal is Aspirin for which the thermodynamics and kinetics of crystallisation were examined.Crystal growth and nucleation kinetic models were developed using non-linear regression.Process models were built for the crystallization process of Aspirin by combining the population balance model with mass balance equtaions.The models were applied to simulate the evolving behaviour of particle size distribution of crystals of Aspirin.In principle,process optimisation techniques were introduced to the proposed models for optimising the product crystal size distribution.Optimal temperature and concentartion profiles leading to the desired crystal size distributions were derived.The orthogonal collocation on finite element method was investigated and found to be an effective optimisation technique for the current application.