Polymorphism in Molecular Crystals and Cocrystals

Abstract

Polymorphism refers to a compound's ability to exist in more than one crystalline modification through variations in the solid-state structures. Over the years, polymorphism has received extensive academic and industrial attention because of its impact on physical and chemical properties of active pharmaceutical ingredients and materials. It is preferable to develop the most stable polymorph to avoid unwanted phase transformation during processing and manufacturing. Therefore, a thorough polymorph screening and complete characterization of all the polymorphs are vital for understanding stability and phase transformations among different polymorphs. Recent advances in screening methodologies and analytical techniques paved ways for successful identification of potential polymorphs. While polymorphism in active pharmaceutical ingredients and single-component crystals is widely studied, such studies in multicomponent crystals such as cocrystals have received significant attention only in recent years. This chapter highlights some recent polymorphic systems of molecular crystals and cocrystals and emphasizes the potential implications of polymorphism in pharmaceutical and materials science. A brief history of polymorphism, factors that control the crystallization of polymorphs, thermodynamic aspects, and recent advances in screening methodologies and analytical techniques are also covered.

Betulin-3,28-diphosphate. Physico-Chemical Properties and In Vitro Biological Activity Experiments

“…Consequently, BDP samples having differences in FTIR spectra, melting temperature and solubility due to intermolecular interactions between the molecules of compounds or the molecules of the solvent and compound, may be considered as different structural forms of BDP [ 16 ].…”

“…Thermoanalytical methods (DSC/TG) are among the most important techniques to take physicochemical measurements and determine multiple structural forms and their phase transitions of a singular chemical entity [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. It has been shown earlier that DSC can reliably characterize the observed phase transition with <5 mg of a tripeptide sample [ 20 ].…”

Chasing the Co-crystal Disappearing Polymorph with Ab Initio Methods

“…Polymorphism in co-crystal solids has been extensively studied in recent years, mainly because of its pivotal role in the understanding of self-assembly phenomena in molecular crystals. , The possibility to predict and control the production of stable and functional co-crystal materials and pharmaceuticals is the Holy Grail of crystal engineering. ,, The recently performed analysis of the Cambridge Structural Database has indicated 600 entries of co-crystal polymorphs with 184 distinct chemical compositions . Among the single and multicomponent organic crystals, the co-crystal group of solids is the only one with increasing number of polymorphic entries, year after year.…”

2D Monomolecular Nanosheets Based on Thiacalixarene Derivatives: Synthesis, Solid State Self-Assembly and Crystal Polymorphism

“…Polymorphism significantly affects the physicochemical properties of materials, such as stability, density, melting point, solubility, bioavailability, etc. [ 9 ]. Hence, characterization of all possible polymorphs, identification of a stable polymorph and the development of a reliable process for sequential production are crucial significance in modern design of pharmaceuticals and materials.…”