Mathematical modeling, simulation, and optimal design of pharmaceutical crystallizers

Crystallization is the most important purification process in the pharmaceutical industry. In addition to purification, this process can generate solid particles for incorporation with excipients into drug products such as tablets with precisely tunable quantities of active pharmaceutical ingredients. The mathematical modeling and simulation of crystallization processes are useful in systems engineering, with the key conservation equation for the particle size distribution being a partial differential equation known as the population balance equation. This thesis constructs population balance models for three distinct particulate processes: 1) the breakage of crystals due to ultrasonication, 2) a semi-batch anti-solvent crystallization, and 3) continuous slug-flow crystallization, which are solved by three distinct simulation methods: 1) breakage matrix with integer arithmetic, 2) method of characteristics, 3) method of moments combined with the method of lines. The population balance models are also employed for three different engineering purposes: kinetics estimation, steady-state process design, and the design of dynamic feedback control structures. Comparisons to experimental data are made where possible to keep the simulations relevant and grounded in reality. Simulations 1 and 3 are the first to simulate their corresponding processes. Simulation 2 provides a method to substantially reduce experimental costs for the estimation of crystallization kinetics that is contrary to the current literature. All three studies employ mathematical models to advance crystallization technology.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Rasche, Michael Lawrence

Contributors dc:contributor

• Braatz, Richard D.
• Kenis, Paul J.A.
• Suslick, Kenneth S.
• Rao, Christopher V.

• crystallizer design
• population balance
• sonofragmentation
• slug flow
• simulation

Statement dc:rights

• Copyright 2015 Michael Rasche

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/78427

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/78427