Formulation of Physicochemical Problems

Modern science and engineering requires high levels of qualitative logic before the act of precise problem formulation can occur. Thus, much is known about a physicochemical problem beforehand, derived from experience or experiment (i.e., empiricism). Most often, a theory evolves only after detailed observation of an event. Thus, the first step in problem formulation is necessarily qualitative (fuzzy logic). This first step usually involves drawing a picture of the system to be studied. 

The third step requires the setting down of finite or differential volume elements, followed by writing the conservation laws. In the limit, as the differential elements shrink, then differential equations arise naturally. Next, the problem of boundary conditions must be addressed, and this aspect must be treated with considerable circumspection. 

When the problem is fully posed in quantitative terms, an appropriate mathematical solution method is sought out, which finally relates dependent (responding) variables to one or more independent (changing) variables. The 

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There are two main problems to consider. One is the formulation of quantitative relationships using physicochemical parameters and regression analysis. As such equations are derived, the problem of organization of the mass of data must be solved. The most suitable, relatively inexpensive method for dealing with the structures of organic compounds via computers is the Wiswesser Line Notation method. This notation and the proper computer program can be of great help in comparative pharmacodynamics. 

Figure 5.14 summarises the physicochemical problems in the use of preservative molecules in formulations. Solubility and partition coefficients of ionised species are determined, as we have seen, by the pH and ionic strength of the system. In this example, partitioning may occur from the aqueous phase to the oily... 

This paper has focused on two recent computer methods for discrete simulation of chemical kinetics. Beginning with the realization that truly microscopic computer experiments are not at all feasible, I have tried to motivate the development of a hierarchy of simulations in studies of a class of chemical problems which best illustrate the absolute necessity for simulation at levels above molecular dynamics. It is anticipated (optimistically ) that the parallel development of discrete event simulations at different levels of description may ultimately provide a practical interface between microscopic physics and macroscopic chemistry in complex physicochemical systems. With the addition to microscopic molecular dynamics of successively higher-level simulations intermediate between molecular dynamics at one extreme and differential equations at the other, it should be possible to examine explicitly the validity of assumptions invoked at each stage in passing from the molecular level to the stochastic description and finally to the macroscopic formulation of chemical reaction kinetics. 

As with clearance, the physicochemical properties of a drug can determine its absorption and hence affect bioavailability. Hydrophilic drugs may dissolve well in the gut lumen and hence cause few formulation problems, but cross cell membranes poorly and hence may be poorly... 

Dissolution of a drug substance is controlled by several physicochemical properties, including solubility, surface area, and wetting properties. For insoluble compounds, dissolution is often the rate-limiting step in the absorption process. Knowledge ofthe dissolution rate of a drug substance is therefore very useful for formulation development. The appropriate dissolution experiments can help to identify factors that contribute to bioavailability problems, and also assist in the selection of the appropriate crystal form and/or salt form. Dissolution tests are also used for other purposes such as quality control and assisting with the determination of bioequivalence (Dressman et al., 1998). 

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