Polymorphism of pharmaceuticals

After discovery of the first cases of polymorphism with dramatic differences in biological activity between two forms of the same drug... no pharmaceutical manufacturer could neglect the problem. (Borka 1991) 

There are many mysteries of nature that we have not yet solved. Hurricanes, for example continue to occur and often cause massive devastation. Meteorologists cannot predict months in advance when and with what velocity a hurricane will strike a specific community. Polymorphism is a parallel phenomenon. We know that it will probably happen. But not why or when. Unfortunately, there is nothing we can do today to prevent a hurricane from striking any community or polymorphism from striking any drug. (Sun 1998) 

---

A Burger, R Ramberger. On the polymorphism of pharmaceuticals and other molecular crystals. I. Theory of thermodynamic rules. Mikrochim Acta (Wein) 2 259-271, 1979. 

Borka, L. Haleblian, J.K. Crystal polymorphism of pharmaceuticals. Acta Pharm. Jugosl. 1990, 40, 71-94. 

Brittain HG. Polymorphism of Pharmaceutical Solids. Marcel Dekker, New York, 1999. 

Brittain HG and Grant DJW. Effects of Polymorphism and Solid-State Solvation on Solubility and Dissolution Rate. In Brittain HG ed.), Polymorphism of Pharmaceutical Solids. Marcel Dekker, New York, 1999, pp. 279-330. 

Guillory JK. Generation of polymorphs, hydrates, solvates and amorphous solids. In Brittain HG, ed. Polymorphism of Pharmaceutical Solids. New York Marcel Dekker, 1999 183-226. 

A Burger, R Ramberger. On the polymorphism of pharmaceuticals and other molecular crystals. I. Theory of thermodynamic rules. Mikrochim Acta [Wien] 11 259— 271, 1979. A Burger, R Ramberger. On the polymorphism of pharmaceuticals and other molecular crystals, n. Applicability of thermodynamic rules. Mikrochim Acta [Wien] 11 273-316, 1979. 

Another important aspect of pharmaceutical analysis is the characterization of the different crystalline forms (polymorphs) of pharmaceutical solids. It is well established that the different forms of a drug can exhibit significantly different physical and chemical properties, and often one form is preferred due to its superior drug activity. An example of how the differences between... 

FIGURE 1.3 A timeline of events concerning solid-state issue with polymorphism of pharmaceutical drugs over past 30 years. Adapted from Lee et al. [9]. Reproduced with permission of Annual Reviews. 

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... 

---