Solubility Advantage of Pharmaceutical Cocrystals

Good, David; Rodrı́guez-Hornedo, Naı́r

doi:10.1021/cg801039j

Cited by 746 publications

(786 citation statements)

References 46 publications

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“…The transition concentration or invariant point was determined using a previously reported method (Good and Rodríguez-Hornedo, 2009). This was achieved by adding excess DBSO to a slightly undersaturated aqueous BA solution and by adding excess cocrystal to a presaturated aqueous DBSO solution.…”

Section: Transition Concentration (C Tr ) Measurementmentioning

confidence: 99%

“…Determination of the solubility of complexes was reported by Higuchi as early as in the 1950's (Higuchi and Connors, 1965). Rodríguez-Hornedo and coworkers have recently developed new theoretical models in order to predict solubility and solution stability of cocrystals (Good and Rodríguez-Hornedo, 2009;Good and Rodríguez-Hornedo, 2010;Nehm S.J. et al, 2006;Reddy L.S.…”

Section: Introductionmentioning

confidence: 99%

“…et al, 2009). It was found that the solubility of cocrystals is strongly dependent on the co-former concentration in the appropriate solvent (Good and Rodríguez-Hornedo, 2009). Therefore, it is important to measure concentrations of both compounds when undertaking the solubility experiment.…”

Section: Introductionmentioning

confidence: 99%

“…Solubility is a relevant parameter that has to be investigated for each cocrystal system since true equilibrium solubility might be difficult to measure due to solid-state transformation in solution (Good and Rodríguez-Hornedo, 2009). Such solution-mediated transformations to the thermodynamically more stable state should result in a change in the dissolution rate and therefore it is important to control/measure these processes.…”

Section: Introductionmentioning

confidence: 99%

“…However, solid-state changes are not the sole rate-determining factors. Surface area, particle size distribution of the drug, fluid dynamics and the experimental apparatus can complicate the interpretation of dissolution results (Good and Rodríguez-Hornedo, 2009). …”

Section: Introductionmentioning

confidence: 99%

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Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Grossjohann

Eccles

Maguire

et al. 2012

International Journal of Pharmaceutics

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This study examined the 1:1 cocrystal benzamide: dibenzyl sulfoxide, comprising the poorly water soluble dibenzyl sulfoxide (DBSO) and the more soluble benzamide (BA), to establish if this cocrystal shows advantages in terms of solubility and dissolution in comparison to its pure components and to a physical mixture. Solubility studies were performed by measuring DBSO solubility as a function of BA concentration, and a ternary phase diagram was constructed. Dissolution was examined through intrinsic dissolution studies. Solid-state characterisation was carried out by powder X-ray diffraction (PXRD), energy-dispersive X-ray diffraction (EDX), infra-red spectroscopy (ATR-FTIR) and thermal analysis. DBSO solubility was increased by means of complexation with BA. For the cocrystal, the solubility of both components was decreased in comparison to pure components. The cocrystal was identified as metastable and incongruently saturating. Dissolution studies revealed that dissolution of DBSO from the cocrystal was not enhanced in comparison to the pure compound or a physical mix, while BA release was retarded and followed square root of time kinetics. At the disk surface a layer of DBSO was found. The extent of complexation in solution can change the stability of the complex substantially. Incongruent solubility and dissolution behaviour of a cocrystal can result in no enhancement in the dissolution of the less soluble component and retardation of release of the more soluble component

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Section: Transition Concentration (C Tr ) Measurementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Grossjohann

Eccles

Maguire

et al. 2012

International Journal of Pharmaceutics

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Crystal Engineering

Tiekink

2012

Supramolecular Chemistry

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Crystal engineering is an emerging discipline whereby practitioners aim to arrange molecules, both organic and metalorganic, in the crystalline phase by rational design. This challenge requires the exploitation of well‐known supramolecular glues such as hydrogen bonding and coordinate bonding. These are augmented by a myriad of nominally weaker and less directional noncovalent interactions that, increasingly, are being demonstrated as important in crystal structure design. Applications in fields as diverse as pharmaceuticals, photoluminescent materials, and metalorganic frameworks for gas storage are some of the motivations for crystal engineering that draw together scientists from a wide range of disciplines. This illustrated overview summarizes factors that dictate the ways molecules aggregate in the solid state, including a description of the diverse types of noncovalent interactions and other crystal packing principles that have being identified as being important in stabilizing crystal structure. Applications of crystal engineering drawn from both the organic and metalorganic realms are discussed. These include cocrystal formation, solid‐state reactions, and metalorganic framework structures. Furthermore, the importance of in silico studies and data mining as they relate to crystal engineering is highlighted throughout.

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Cocrystals: Synthesis, Structure, and Applications

Aakeröy

Chopade

2012

Supramolecular Chemistry

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The crystal structure of a compound, the 3D orientation and organization of molecules in a highly regular manner, ultimately determines most of the fundamental physical properties of that particular material, for example, thermal stability, hygroscopicity, conductivity, and mechanical strength. Consequently, an ability to control and change the crystalline environment of a material without altering the molecular properties would be of enormous significance to both manufacturers and consumers of solid specialty chemicals such as pharmaceuticals, pigments, energetic materials, toxins, foodstuff, and detergents. Preparation of cocrystals—homogeneous crystalline solids composed of different molecular building blocks—offers an additional path for incorporating functional molecules, active ingredients, within a crystalline casing, but the synthetic challenges associated with supramolecular synthesis are numerous and nontrivial. This chapter describes several strategies for the assembly of cocrystals using hydrogen bonds and halogen bonds and provides a more in‐depth examination of how the electrostatic charge on individual attempts can be used to control efficiency and selectivity of supramolecular synthesis. Finally, a few examples of applications of cocrystals in pharmaceutical sciences are discussed.

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Solubility Advantage of Pharmaceutical Cocrystals

Cited by 746 publications

References 46 publications

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Crystal Engineering

Cocrystals: Synthesis, Structure, and Applications

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