Grants and Contributions:

Grant or Award spanning more than one fiscal year (2017-2018 to 2018-2019).

Crystallization is one of the oldest separation and purification unit operations in chemical industry. During thisx000D
process, the atoms or molecules are transferred from solution to the solid phase and form solid crystals.x000D
Conventionally, crystallization of fine chemicals and pharmaceuticals is conducted in batch mode to allowx000D
flexibility to respond to varying customized design requirements and changing market demands; however, thisx000D
approach can also lead to increased manufacturing costs and batch-to-batch variations in product quality.x000D
Recently, the development of continuous manufacturing and crystallization techniques has received increasingx000D
interest and research effort from academic and industrial sectors, due to the potential advantages of reducedx000D
costs, shorter development time, more robust scale-up and improved control performance.x000D
Imatinib mesylate is a potent and selective inhibitor of the protein tyrosine kinase developed by Novartis. Itx000D
was approved under the trade name "Gleevec/Glivec" by the US Food and Drug Administration (FDA) to treatx000D
Philadelphia chromosome positive chronic myelogenous leukemia (CML) in blast crisis, accelerated phase, orx000D
chronic phase after failure of interferon-alpha therapy and kit (CD117) positive unrespectable and/or metastaticx000D
malignant Gastro Intestinal Stromal Tumors (GISTs).x000D
Apotex PharmaChem Inc., as a generic pharmaceutical company is developing a continuous process for thex000D
manufacture of imatinib mesylate from 2018 when the patent of this drug is released.x000D
The objective of this proposal is to design an effective continuous crystallization process for the production ofx000D
this pharmaceutical from an organic solvent. The target crystal form is the metastable form with proper crystalx000D
size distribution. The metastable form is hygroscopic with needle like habit.x000D
During the course of the project, the solubility of imatinib mesylate in a series of organic solvents and theirx000D
mixture will be measured for solvent screening. The polymorphic transformation and nucleation and growthx000D
kinetics will be measured in a continuous mixed suspension mixed product removal crystallizer.