Continuous separation of conglomerate forming enantiomers using crystallization process

Enantiomers are the results of chirality or handedness of molecules which are the non-superimposable mirror images of each other. Enantiomers are widely found in organic compounds and their separation is a major concern in the modern pharmaceutical, food and agricultural industries. Separation of the enantiomorphs is particularly important in the pharmaceutical industry, since very often one of the enantiomers exhibits the intended therapeutic activity while the other is inert or toxic. For example, S (-)-fluoxetine shows remarkable therapeutic effects in preventing migraines, while the racemic (equimolar mixture of both enantiomers) drug (the antidepressant Prozac) has no effect. Thus, it is demanded by the regulating authorities that the chiral drugs are administered in an optically pure form. This stringent regulatory policy has led to intensified efforts in industrial and academic research to develop processes that are able to produce pure enantiomers. Various means available for resolution of enantiomers includes classical chiral separation techniques such as preferential crystallization, chromatography, membrane separation. Among various means, preferential crystallization is an attractive and efficient way to separate the racemic mixtures since typically no auxiliaries and reagents other than solvent are needed. Crystallization can be carried out in standard equipment readily available in the pharmaceutical and fine chemical industries. Traditionally the crystallization processes in the industry are dominated by the batch processes which have suffered from batch-to- batch variability, particularly at the manufacturing scale. In contrast, continuous crystallizer when operated under a controlled steady state, the crystallization process in theory provides no variability in temperature, concentration, crystal size distribution (CSD), etc. over time, leading to greater reproducibility when compared with batch methods. In this project, we would like to address the problem of separation of enantiomers in continuous crystallization configurations which will contribute towards the continuous manufacturing of pharmaceutical products.

The aim of this project is the design, model development, simulation and optimization of novel continuous crystallization processes that allows continuous and efficient separation of the conglomerate forming enantiomers. Various innovative process configurations in plug flow crystallizer will be investigated. A population balance based model coupled with mass and energy balance equations will be used in this purpose. A model based optimization framework will be developed to find optimum process variables such as feed rate, temperature profile and seed loading. Simulation and optimization of the process will be carried out using MATLAB computing software. This study will serve as the theoretical basis to design the novel crystallization process configurations and building experimental setup for continuous separation of enantiomers.

The successful candidate should have (or expect to achieve) a minimum of a UK Honours degree at 2.1 or above (or equivalent) in Chemical Engineering or a similar discipline.

Knowledge or interest in process design, simulation and experience in computer programming would be advantageous

APPLICATION PROCEDURE:

Formal applications can be completed online: http://www.abdn.ac.uk/postgraduate/apply. You should apply for Degree of Doctor of Philosophy in Chemical Engineering, to ensure that your application is passed to the correct person for processing.

NOTE CLEARLY THE NAME OF THE SUPERVISOR AND EXACT PROJECT TITLE YOU WISH TO BE CONSIDERED FOR ON THE APPLICATION FORM.

Informal inquiries can be made to Dr A Majumder ([Email Address Removed]) with a copy of your curriculum vitae and cover letter. All general enquiries should be directed to the Postgraduate Research School ([Email Address Removed]).