Pharmaceutical Applications of Polymorphism

Haleblian, John K.; McCrone, Walter C.

doi:10.1002/jps.2600580802

Cited by 792 publications

(442 citation statements)

References 38 publications

(6 reference statements)

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“…log Sϭ(ϪDH soln /2.303R)(1/T)ϩC (1) where S is the solubility, DH soln is the heat of solution, R is the gas constant and C is a constant. In previous studies, [9][10][11][12][13][14][15] this equation has been widely applied for the estimation of transition temperature for the enantiotropic polymorphic pairs.…”

Section: Theoreticalmentioning

confidence: 99%

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A Novel Method for Estimation of Transition Temperature for Polymorphic Pairs in Pharmaceuticals Using Heat of Solution and Solubility Data.

Urakami

Shono

Higashi

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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Section: Theoreticalmentioning

confidence: 99%

“…1,3,4) In addition, the relative thermodynamic stability of the polymorphs has also been of great interest. Polymorphs fall into one of two categories: a monotropic system or an enantiotropic system.…”

mentioning

confidence: 99%

A Novel Method for Estimation of Transition Temperature for Polymorphic Pairs in Pharmaceuticals Using Heat of Solution and Solubility Data.

Urakami

Shono

Higashi

et al. 2002

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Small organic molecules show a high probability of crystallising in multiple crystal forms, which may differ in physico-chemical characteristics such as melting point or solubility. [9][10][11][12] The latter characteristic is especially important for pharmaceuticals, as solubility and especially water solubility is directly linked to bioavailability of the drug compound and thus its pharmacological activity in patients.…”

Section: Introductionmentioning

confidence: 99%

Influence of Bio-Isosteric Replacement on the Formation of Templating Methanol and Acetonitrile Solvates in Lophines

Kitchen

Melvin

Najib

et al. 2016

Crystal Growth & Design

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Bio-isosteric replacement is a frequently used tool in medicinal chemistry. While the pharmacological activity is not influenced by the exchange of substituents, the solid-state characteristics and formation of different crystal forms may well be altered dramatically, jeopardizing the processability and safety of the drug compound. In this study we investigate a series of triphenylimidazole (TPI) derivatives as model compounds with the bio-isosteric exchange of only one halogen position (F, Cl, Br, I). Crystallization from two industrially used solvents (methanol and acetonitrile) reveals solvate formation of all TPIs, for which the basic hydrogen bonded motif does not change. The three-dimensional packing depends on the size of the substituent and changes from fluoroto chloro-and bromo-substitution but remains the same for the larger iodo-substituent. From acetonitrile, only F-TPI and Cl-TPI form an isomorphic channel solvate, which in both cases desolvates reversibly to an isomorphic crystal form. Due to the halogen atom lining of the channels, bromine and iodine are too large to generate a stable packing. This study illustrates the importance of understanding the influence of bio-isosteric substitution on the solid state, in order to best utilize this common tool.

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“…Since Cardew & Davey (1985) presented the first analysis of the kinetics of 'solvent-mediated phase transformations', it has become clear that such transformations play a key role in the mineralogical evolution of the Earth's crust, as well as in a wide range of industrial processes, including control of cement hydration (Tzschichholz et al 1996) and production of nano-structured devices (Sun & Xia 2004;Xia et al 2009). Pharmaceuticals and explosives often exhibit polymorphism, and they may transform from one crystal structure to another during storage and/or processing (Haleblian & McCrone 1969;Achuthan & Jose 1990;Rodriguez-Hornedo & Murphy 1999;Dharmayat et al 2008;Heinz et al 2009). This is important because the solubility, rate of dissolution, bioavailability, melting point and chemical stability of pharmaceuticals depend on the physical form and the crystal structure of the pharmaceutical, and because the processing behaviour, including compressibility and granular flow, varies from polymorph to polymorph.…”

Section: Introductionmentioning

confidence: 99%

The mechanism of porosity formation during solvent-mediated phase transformations

et al. 2010

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Solvent-mediated solid-solid phase transformations often result in the formation of a porous medium, which may be stable on long time scales or undergo ripening and consolidation. We have studied replacement processes in the KBr-KCl-H 2 O system using both in situ and ex situ experiments. The replacement of a KBr crystal by a K(Br,Cl) solid solution in the presence of an aqueous solution is facilitated by the generation of a surprisingly stable, highly anisotropic and connected pore structure that pervades the product phase. This pore structure ensures efficient solute transport from the bulk solution to the reacting KBr and K(Br,Cl) surfaces. The compositional profile of the K(Br,Cl) solid solution exhibits striking discontinuities across disc-like cavities in the product phase. Similar transformation mechanisms are probably important in controlling phase-transformation processes and rates in a variety of natural and man-made systems.

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Pharmaceutical Applications of Polymorphism

Cited by 792 publications

References 38 publications

A Novel Method for Estimation of Transition Temperature for Polymorphic Pairs in Pharmaceuticals Using Heat of Solution and Solubility Data.

A Novel Method for Estimation of Transition Temperature for Polymorphic Pairs in Pharmaceuticals Using Heat of Solution and Solubility Data.

Influence of Bio-Isosteric Replacement on the Formation of Templating Methanol and Acetonitrile Solvates in Lophines

The mechanism of porosity formation during solvent-mediated phase transformations

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