Cimetidine design

This final Pures step is the last stage of manufacture for the API and may be considered as the API Product design step. It will be the focus of this chapter s case study, using the generic drug molecule Cimetidine as an example. 

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. 

Case Study - Solubility Modelling and Crystallization Process Design for Cimetidine... 

Cimetidine Crystallization Process Design with NRTL-SAC. 

NRTL-SAC has been demonstrated through the case study on Cimetidine as a valuable aid to solubility data assessment and targeted solvent selection for crystallization process design. The average model error is typically 0.5 Ln (x) [1] and is sufficient as a solvent screening tool. Methods that can deliver greater accuracy would increase the value and utility of these techniques. It is impressive in the case of Cimetidine that the NRTL-SAC correlation is capable of reasonable accuracy and predictive capability on the basis of just 2 fitted parameters. Further work to extend the solvent database and optimize the descriptive parameters will be beneficial, and are planned by the developers. 

Tn Chapter 43 we mentioned the role of histamine in promoting acid secretion in the stomach, and its role in causing gastric ulcers. The drug cimetidine was designed to counteract the effect of histamine. Histamine is produced in the body by decarboxylation of histidine using the mechanism you have just seen. 

Mast cells and enterochromaffin-like cells found in the interstitium and among parietal cells contain histamine, which acts on parietal cell receptors to stimulate the release of hydrochloric acid. The histamine receptor on parietal cells is designated as H2 and is blocked by H2 blockers such as cimetidine which are widely used to treat peptic ulcers. 

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