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dc.contributor.authorSmith, Geoffen
dc.contributor.authorPedge, Nicholasen
dc.contributor.authorKhan, Karrar Aen
dc.contributor.authorBukhari, Nadeem Irfanen
dc.contributor.authorHussain, Amjaden
dc.contributor.authorErmolina, I.en
dc.date.accessioned2018-11-02T11:34:42Z
dc.date.available2018-11-02T11:34:42Z
dc.date.issued2018-08-02
dc.identifier.citationHussain, A., Smith, G., Khan, K.A., Bukhari, N.I., Pedge, N.I., Ermolina, I. (2018) Solubility and dissolution rate enhancement of ibuprofen by co-milling with polymeric excipients. European Journal of Pharmaceutical Sciences. 123, pp. 395-403en
dc.identifier.urihttp://hdl.handle.net/2086/17043
dc.descriptionThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.en
dc.description.abstractThe aim of this study was to enhance the kinetic solubility and dissolution rate of ibuprofen by co-milling with different excipients and to establish the underlying mechanism(s) for such enhancement. In the first-part, two excipients (HPMC and soluplus) were selected from seven, and the optimal ball-milling parameters of speed and time (18 Hz, 15 min) were determined based on solubility-enhancement and flow-ability criteria. In the second-part, co-milling of different weight-ratios of ibuprofen-to-excipient was carried out and solubility and dissolution rates were determined. Mechanisms of biopharmaceutical enhancement were studied by SEM, laser diffraction, DSC, and FTIR analysis of the co-mixtures. Ibuprofen solubility (0.09 mg/mL for un-milled) was increased by factors of 4–5 and 10–20 for HPMC and soluplus, respectively. The weakening of crystals, stabilization of the amorphous phase and an increase in solid-state hydrogen bonding are the likely mechanisms for this enhancement. Reductions in Q70% dissolution time were also observed, by a factor of 4 and 7 for ibuprofen:HMPC and ibuprofen:soluplus co-milled mixtures, respectively. Although, there were similar reductions in particle size, dispersibility and degree of amorphization in both mixtures, the higher dissolution rate for soluplus, over that for HPMC, must be due to the additional solubilization contribution to the kinetic solubility provided by soluplus.en
dc.language.isoenen
dc.subjectPoor soluble drugsen
dc.subjectBall millingen
dc.subjectSolubility enhancementen
dc.subjectDissolution rateen
dc.subjectParticle sizeen
dc.subjectAmorphous contenten
dc.titleSolubility and dissolution rate enhancement of ibuprofen by co-milling with polymeric excipientsen
dc.typeArticleen
dc.identifier.doihttps://doi.org/10.1016/j.ejps.2018.08.001
dc.peerreviewedYesen
dc.explorer.multimediaNoen
dc.funderN/Aen
dc.projectidN/Aen
dc.cclicenceCC-BY-NCen
dc.date.acceptance2018-08-01en
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en


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