Pharmaceutical industry applications polymorphism

The most widely used application of solid state NMR in the pharmaceutical industry is in the area of polymorphism, or pseudopolymorphism, and this will be the focus of this section. 

Raman spectroscopy is emerging as a powerful analytical tool in the pharmaceutical industry, both in PAT and in qualitative and quantitative analyses of pharmaceuticals. Reviews of analyses of pharmaceuticals by Raman spectroscopy have been published.158 159 Applications include identification of raw materials, quantification of APIs in different formulations, polymorphic screening, and support of chemical development process scale-up. Recently published applications of Raman spectroscopy in high-throughput pharmaceutical analyses include determination of APIs in pharmaceutical liquids,160,161 suspensions,162 163 ointments,164 gel and patch formulations,165 and tablets and capsules.166-172... 

F. Laplant and A. De Paepe, Raman spectroscopy for identifying polymorphs, in Pharmaceutical Applications of Raman Spectroscopy, S. Sasic (Ed), Technology for the Pharmaceutical Industry Series, John WUey Sons, Ltd, Hoboken, 2008. 

Nevertheless, this observation cannot be reproduced because of the polymorphic changes that occur when the drug is stored. Until the challenge of controlling or stabilizing the polymorphism conversion is met, the application of polymorphism in pharmaceuticals will be questionable. The knowledge and data on polymorphism are important to the pharmaceutical industry. Many pharmaceutical problems can be explained or avoided if the concept of polymorphism is understood and methods of detection, control, purification, and isolation are available. 

Thermal analysis is an extremely important analytical tool for the pharmaceutical industry. All transitions in materials involve the flow of heat (either into the sample during an endothermic event or out of the sample during an exothermic event) and DSC is the universal detector for measuring a wide variety of transitions in pharmaceutical materials. These include measurement of amorphous structure, crystallinity (and polymorphs), drug-excipient interaction and many other applications. 

Other applications of DSC and other TA techniques to the pharmaceutical industry include physico-chemical interactions (275), polymorphism in triglyceride suppository formulations (276) drug-excipient interactions (277), and many more. Reviews of the applications of DTA/DSC and different techniques to pharmaceuticals include those by Brennan (278), Daly (279), and others (280). 

Polymorphism plays a crucial role in the preparation of active pharmaceutical ingredients (APIs), and the possibility to predict and control the crystallization of a specific polymorph is today of great interest for many applications in the pharmaceutical industry. Although identical in their chanical composition, different polymorphs often exhibit important differences in solnbility, dissolution rate, stability, melting point, density, and many other properties that significantly affect the efficacy, bioavailability, and safety of APIs (Llinas and Goodman 2008). 

Many membrane separation applications have already benefitted from membrane modification strategies. Chapter 10 describes how bespoke polymeric membranes have been used to improve the crystallization of biomolecules. Membrane crystallization allows through a careful control of the process parameters the production of crystals with controlled shape, size, size distribution, and polymorphism. Further research is required to provide comprehensive understanding of the complex relationships between membrane process parameters and crystal structure. The control of product polymorphism will continue to be important in the pharmaceutical industry, which, as the range of drugs and their specificity increase, will reqnire improved... 

As stated in Section 5.1, all solid-state properties of different polymorphs will be different. Which of these parameters is of special importance for a particular type of industry and a particular application can vary. While color is probably the most important parameter of a pigment, taste and feel are decisive for foods, density for explosives, solubility, processability and stability in the pharmaceutical industry, and so on. In any case, it is imperative for aH industries that all possible forms are known and characterized, since the unexpected appearance of a new form may have very serious consequences. An example for that is the well-known Norvir Case [30], where the thermodynamically stable form was found only long after the product was on the market. Subsequently, the original metastable form could not be produced anymore and a new formulation for the product had to be developed [31] causing very high costs. 

---