10 relevant articles about polymorphism and polymorph screening of pharmaceuticals

Publications
No.TopicPublicationComments
1BackgroundOn the polymorphism of pharmaceuticals and other molecular crystals. A. Burger and R. Ramberger. Microchimica Acta. 1979. II. 259-271. Very thorough introduction into the thermodynamics of polymorphism. Introducing various “rules” for polymorphic transformations. Excellent background article – but very theoretically so if you just want “an overview” it might not be the best place to start.
2BackgroundDisappearing Polymorphs.J.D. Dunitz and J. Bernstein. Acc. Chem. Res. 1995. 28. 193-200Interesting article describing the fascinating world of crystallization – given many historical examples of cases where the outcome was different than expected.
3Polymorph screeningCrystallisation of polymorphs: Thermodynamic insight into the role of solvent. T. Threllfall. Org. Process Research & Development. 2000. 4.384-390. (link to article) Crystallisation of polymorphs can be controlled either by thermodynamics or kinetics. The article explains how it is possible to trap metastable polymorphs by controlling concentration and temperature.
4Polymorph screeningGrouping solvents by statistical analysis of solvent property parameters: Implication to polymorph screening. C-h. Gu. H. Li. R.B. Gandhi. K. Raghavan. Int. J. Pharmaceuticals. 2004. 283. 117-125. (link to article)In polymorph screening you want to use solvents with diverse properties in order to obtain as many different crystallization possibilities as possible. This article gives a statistical description of solvent properties – dividing the solvents in classes – and summarizing the individual solvents properties. From this list it is easier to choose the optimal solvents for a screening.
5Polymorph screeningPolymorphism and crystallization of active pharmaceutical ingredients. J. Lu & S. Rohabi. Current Medicinal Chemistry. 2009. 16. 884-905. (link to article)This publication discusses the thermodynamics and kinetics of polymorphic systems. The characterization of polymorphs. and the transformation between polymorphs. The major techniques for polymorph discovery and control developed in the past years are discussed as well.
6Polymorph screeningAn approach to solvent screening for crystallization of polymorphic pharmaceuticals and fine chemicals. M. Mirmehrabi & S. Rohani. J. Pharm. Sciences. 2005. 94 (7). 1560-1576. (link to article)More about the solvent properties in relation to polymorph screening. Selection of the right solvent might be crucial for the outcome of a polymorph screening. This article gives an insight into the parameters that should be considered.
7Polymorph screening Polymorphism in Processes of Crystallization in Solution: A Practical Review. D. Mangin. F. Puel. S. Veesler. Organic Process Research and Development. 2009. 13 (6). 1241-1253.  (link to article) Preferential formation of a polymorph and size depend strongly on the kinetics of the mechanisms involved.  Recent developments in the determination of the kinetics of solution-mediated phase transition are reviewed. The advantages and drawbacks of using process analytical technologies to monitor such transitions are discussed.
8Polymorph screening Crystalline solids. S. Vippagunta. H. Brittain. D. Grant. Advanced Drug Delivery Review. 2001. 48 (1). 6-26.  (link to article) Focus on understanding the origins of polymorphism at the molecular level – and predicting and preparing the most stable polymorph of a drug. Advances in computational tools are described.
9Examples from real lifePolymorphisms and Patent. Market. and Legal Battles: Cefdinir Case Study. W. Cabri . P.Ghetti . G. Pozzi and M. Alpegiani. Organic Process Research & Development. 2007. 11. 64-72. (link to article)Inspiring article describing how polymorphism has been used in patent fights! States the importance of knowing your polymorphs – and protecting them.
10Examples from real lifeCrystal polymorphism in chemical process development. A.Y. Lee. D. Erdemir. A. S. Myerson. Ann. Rev. Chem. Biomol. Eng. 2. 2011. (link to article)Very interesting examples from real life: Cases where polymorphic issues have given rise to regulatory concerns – including the Ritonavir-story.