Pharmaceutical crystals, design

Braun, B. Groen, H. Tschernjaew, J. Production-scale particle design of a pharmaceutical intermediate. Crystal Growth Design 2004, 4 (5), 915-920. 

An example of CAPE tool application to HTE in pharmaceutical design is the use of CBR for identifying the required conditions for protein crystallization. The application of HTE and CAPE to drug development in the context of knowledge discovery is presented in RefP ... 

Zhou, X., M. Fujiwara, X.Y. Woo, E. Rusu, H.H. Tung, C. Starbuck, O. Davidson, Z.H. Ge, and R.D. Braatz (2006). Direct design of pharmaceutical antisolvent crystallization through concentration control. Crystal Growth Design 6, 892—898. 

The application of MM tools in the crystallization and design of pharmaceutical products is described in Chapter 5. 

Mathews and Rawlings (1998) successfully applied model-based control using solids hold-up and liquid density measurements to control the filtrability of a photochemical product. Togkalidou etal. (2001) report results of a factorial design approach to investigate relative effects of operating conditions on the filtration resistance of slurry produced in a semi-continuous batch crystallizer using various empirical chemometric methods. This method is proposed as an alternative approach to the development of first principle mathematical models of crystallization for application to non-ideal crystals shapes such as needles found in many pharmaceutical crystals. 

Togkalidou, T., Braatz, R.D., Johnson, B.K., Davidson, O. and Andrews, A., 2001. Experimental design and inferential modelling in pharmaceutical crystallization. American Institution of Chemical Engineers Journal, 47(1), 160-168. 

The approach in crystal engineering is to learn from known crystalline structures of, for example, minerals in order to design compounds with desired properties. Crystal engineering is considered to be a key new technology with applications in pharmaceuticals, catalysis, and materials science. The structures of adamantane and other diamondoids have received considerable attention in crystal engineering due to their molecular stiffness, derivatization capabilities, and their six or more linking groups [114-117]. 

The Role of Solubility Modeling and Crystallization in the Design of Active Pharmaceutical Ingredients... 

The non-random two-liquid segment activity coefficient model is a recent development of Chen and Song at Aspen Technology, Inc., [1], It is derived from the polymer NRTL model of Chen [26], which in turn is developed from the original NRTL model of Renon and Prausznitz [27]. The NRTL-SAC model is proposed in support of pharmaceutical and fine chemicals process and product design, for the qualitative tasks of solvent selection and the first approximation of phase equilibrium behavior in vapour liquid and liquid systems, where dissolved or solid phase pharmaceutical solutes are present. The application of NRTL-SAC is demonstrated here with a case study on the active pharmaceutical intermediate Cimetidine, and the design of a suitable crystallization process. 

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