Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Chemical and Biochemical Engineering

Supervisor

Sohrab Rohani

Abstract

In this project, the aim was to achieve two important objectives and solve some challenges that the pharmaceutical industry is facing. It will be shown that the NRTL-SAC (Non-random Two Liquid Segment Activity Coefficient) model can best predict the solubility of different pharmaceutical and chemical components in pure and mixed solvents by comparing the results with the well-known model of the UNIFAC. The four parameters that are used in the NRTL-SAC model will be found through nonlinear parameter estimation technique. This project also covers the VLE, LLE, and VLLE phase behaviour calculations using the mentioned models to verify their applicability in industries that use solvents as their main process materials (such as pharmaceutical processes). It will be explained that the NRTL-SAC model is efficient and less complex than the UNIFAC model when dealing with multi-component systems of solvents. The solvent screening process is then modeled using a novel method of modeling and optimization which resulted in a significant change in the objective functions from single to binary solvent combinations. The proposed method shows the efficient selection of single, binary, and ternary solvent systems with the optimal crystallization operating conditions to achieve the desired objectives. However, the change from binary to ternary system of solvents did not have a significant effect on the performance functions. The study on the crystallization process of a polymorphic transformation phenomenon is another part of the project which was modeled and optimized. The novel method of modeling for polymorphic transformation of L-glutamic acid enabled us to develop an optimal control strategy of the system consisting of a variety of process conditions (such as seeded and un-seeded crystallization). The outcome of this part of the project gives a detailed understanding of polymorphic transformation systems with optimal conditions that can be implemented for such processes. Finally some useful experimental work that has been done in the area of nucleation and polymorphic transformation of L-glutamic acid using a powerful spectroscopic probe (Lasentec FBRM) will be explained. The nucleation detection and the change from metastable polymorph to the stable one can be performed using the in-situ FBRM which was used in this project.

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