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. 2009 Jun 3;9(6):2950-2967.
doi: 10.1021/cg900129f. Epub 2009 Apr 20.

Pharmaceutical Cocrystals and Their Physicochemical Properties

Nate Schultheiss  1 , Ann Newman
Affiliations

Pharmaceutical Cocrystals and Their Physicochemical Properties

Nate Schultheiss et al. Cryst Growth Des. .

Abstract

This review article will highlight and discuss the advances made over the last 10 years pertaining to physical and chemical property improvements through pharmaceutical cocrystals and, hopefully, draw closer the fields of crystal engineering and pharmaceutical sciences.

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Figures

Figure 1
Figure 1
Pictures displaying the more common solid-state strategies and their respected components.
Figure 2
Figure 2
Possible multicomponent systems: cocrystals, salt cocrystals, and salts along with their respective solvate/hydrate forms.
Figure 3
Figure 3
Example flowchart for choosing a cocrystal candidate.
Figure 4
Figure 4
Melting points of AMG517 cocrystals and their respected coformers (left); melting onset of coformer versus cocrystal (right). Modified table and graphic from ref (37). Copyright 2008 American Chemical Society.
Figure 5
Figure 5
Solubility and Log Smax values for AMG517 cocrystals (left); Smax as a function of cocrystal melting point (right). Modified table and graphic from ref (37). Copyright 2008 American Chemical Society.
Figure 6
Figure 6
Plot of the solution stability of pharmaceutical cocrystals versus the estimated aqueous solubility of the corresponding coformer.
Figure 7
Figure 7
Schematic of a solubility curve due to a form change and precipitation of a less stable form (curve A); at equilibrium, the curve will level out to the solubility of the less soluble form. Curve B represents the less soluble form.
Figure 8
Figure 8
Intrinsic dissolution profile of fluoxetine HCl and its cocrystals measured in water at 10 °C. (Top ⧫) fluoxetine HCl/succunic acid cocrystal; (middle ◼) fluoxetine HCl; (middle ▲) fluoxetine HCl/fumaric acid cocrystal; (bottom ●) fluoxetine HCl/benzoic acid cocrystal. Figure modified from ref (12).
Figure 9
Figure 9
Polymorphic cocrystals of 1:1 carbamazepine/saccharin.(77)
See this image and copyright information in PMC

References

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    1. Molecules from the “generally regarded as safe” GRAS list, pharmaceutical excipients, amino acids, food additives

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