Pharmaceutical applications thermodynamic analysis

BeUantone RA, Patel P, Sandhu H, Choi D, Singhal D, Chokshi H, Malick AW, Shah NH (2012) A method to predict the equilibrium solubility of dmgs in solid polymers near room temperature using thermal analysis. J Pharm Sd 101 4549-4558 Burger A, Ramberger R (1979) On the polymorphism of pharmaceutical and other molecular crystals I. Theory of thermodynamic rules. Mikrochimica Acta 11 259-281 Chiou WL, Riegelman S (1971) Pharmaceutical applications of solid dispersion systems. J Pharm Sd 60 1281-1302... 

Thermal analysis methods are widely used in all fields of pharmaceutics. They are unique for the characterization of single compounds. The information correlated with the thermodynamic phase diagrams is extremely helpful for rational preformulation and development of new delivery systems. Very rapid and requiring only very small samples of material, these methods are applicable in development and also in production for quality control. The combination with spectroscopic and crystallographic data will allow better insight in complex phase changes behavior. 

As mentioned at the beginning of the chapter, it is not feasible to cover all aspects of the pharmaceutical uses of DSC in the space available hence, emphasis has been placed on what are probably the most important applications of the technique. Clearly, DSC may be used as a simple screening method, for example, in the identification of polymorphs or glass transitions. However, there are numerous ways in which the approach can yield a more sophisticated analysis with comparatively little additional effort. Examples outlined here include the predictability of the thermodynamic parameters associated with polymorphic transitions and the assessment of the relaxation behavior of glassy pharmaceuticals. Both these examples have very tangible practical implications for the prediction of stability hence, such studies are not simply academic exercises but may be of considerable benefit in formulation optimization. 

Every two years, a fundamental review on thermal analysis is published in Analytical Chemistry, in which the development of new methods and the main applications to calibration, thermodynamics, kinetics, polymers, inorganics, pharmaceutical, biological, foods, etc. are reported [1-3]. Several articles regarding coordination compounds are cited and critically described. An update of the applications of evolved gas analysis (EGA), coupled to the thermoanalytical instruments, is also published every four years, and many studies on coordination compounds are cited [4-7]. 

In ord to optimize the applications of SSI technique different problems should be solved with the help of experimental determinations coupled widi some theoretical analysis. It is obvious that the polymer in contact with the supercritical fluid swells (the CO2 dissolves in the polymer) and the extent of swelling depends from the pressure. When the polymer is in contact with the supercritical fluid saturated with the pharmaceutical the solvent again diffuses in the polymer, it swells the polymer and in this way the solubilization of the drug in the polymer is fricilitated. As a consequence in addition to the kinetic problems (diffusion in the polymer matrix) the thermodynamic description of the ternary systems, supa critical fluid, pharmaceutical and polymer, is essential. 

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