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

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Grossjohann, Christine
Eccles, Kevin S.
Maguire, Anita R.
Lawrence, Simon E.
Tajber, Lidia
Corrigan, Owen I.
Healy, Anne Marie
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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.
Intrinsic dissolution , Solubility , Complexation , HPLC , Indomethacin-saccharin cocrystals , Pharmaceutical cocrystals , Phase-diagrams , Rotating disk , Cocrystal , Acid , Bioavailability , Composites , Gabapentin , Apparatus
Grossjohann, C., Eccles, K.S., Maguire, A.R., Lawrence, S.E.,Tajber, L., Corrigan, O.I., Healy, A.M. (2012) 'Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal'. International Journal of Pharmaceutics, 422 :24-32.
Copyright © 2012, Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in International Journal of Pharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in International Journal of Pharmaceutics, [422, January 2012]