Solid-state characterization preformulation studies

Solid-state characterization is one of the most important functions of the preformulation group, which is assigned the responsibility of making recommendations for further formulation work on a lead compound. Physical properties have a direct bearing on both physical and chemical stabilities of the lead compound. Much of the later work on formulation will depend on how well the solid state is characterized from the decisions to compress the drug into tablets to the selection of appropriate salt forms. The studies reported in this section, of course, apply to those drugs that are available in solid form, crystalline or amorphous, pure or amalgamated. 

Additional preformulation and physicochemical characterization of the candidate compound are performed and stress stability studies may be initiated. Ideally, the optimal solid state (polymorphic) and chemical (salt) form of the molecule are identified as part of clinical candidate selection. Selection of the most stable and bioavailable form will expedite subsequent development. The methods for testing the drug substance are refined and additional methods may be developed. 

There is no doubt that isothermal microcalorimetry has the potential to be very useful in studies of chemical degradation. The success will be greatest for solution-state reactions for which the reacting concentration is known, but even these can be limited by physical artifacts by, for example, the slow diffusion of oxygen into the liquid from the head space. The use of this technique for solid-state reactions is certainly not impossible, but is an area where great care is needed. The technique may therefore be used readily in a preformulation environment for solution systems, but is perhaps better applied in a QC (quality control) role for well-characterized solid-state processes. 

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