Compartmental population kinetics

The model is able to predict the influence of mixing on particle properties and kinetic rates on different scales for a continuously operated reactor and a semibatch reactor with different types of impellers and under a wide range of operational conditions. From laboratory-scale experiments, the precipitation kinetics for nucleation, growth, agglomeration and disruption have to be determined (Zauner and Jones, 2000a). The fluid dynamic parameters, i.e. the local specific energy dissipation around the feed point, can be obtained either from CFD or from FDA measurements. In the compartmental SFM, the population balance is solved and the particle properties of the final product are predicted. As the model contains only physical and no phenomenological parameters, it can be used for scale-up. 

Lunn, D.J., Best, N., Thomas, A., Wakefield, J., and SpiegeUialter, D. 2002. Bayesian analysis of population PK/PD models general concepts and software. /. Pharmacokinet. Pharmacodynam. 29 271-307. Magni, R, BeUazzi, R., Nauti, A., Patrini, C., and Rindi, G. 2001. Compartmental model identification based on an empirical Bayesian approach the case of thiamine kinetics in rats. Med. Biol Eng. Comput. 39 700-706. 

Models of secondary kinetic processes were considered in detail Chapters 5 and 6 whilst accounting for poor mixing effects by use of CFD-based methods were described and illustrated in Chapters 2 and 8. Such CFD codes can be linked via compartmental and mixing models, or coupled directly with the population balance if the precipitation processes are particularly fast in comparison to the mixing process. 

Our main focus is the quantitative understanding of compartmentalized gene expression with respect to the internal solute distribution. By testing different entrapment mechanisms and their effect on protein production in the different PS processes, it is possible to create a link between an observable feature (protein production) and the internal liposomal solute distribution. The ability to infer the precise internal vesicle content is of course of great interest for understanding the different kinetics in different size compartments. This means that the ideal experimental approaches are those able to perform single vesicle measurements, as population measurements could be unable to characterize the high complexity of vesicles behavior. 

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