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dc.contributor.authorMohammad, Mohammad A.*
dc.contributor.authorGrimsey, Ian M.*
dc.contributor.authorForbes, Robert T.*
dc.date.accessioned2015-07-21T11:37:20Z
dc.date.available2015-07-21T11:37:20Z
dc.date.issued2015-10-10
dc.identifier.citationMohammad MA, Grimsey IM and Forbes RT (2015) Mapping the solid-state properties of crystalline lysozyme during pharmaceutical unit-operations. Journal of Pharmaceutical and Biomedical Analysis. 114: 176–183.en_US
dc.identifier.urihttp://hdl.handle.net/10454/7363
dc.descriptionNoen_US
dc.description.abstractBulk crystallisation of protein therapeutic molecules towards their controlled drug delivery is of interest to the biopharmaceutical industry. The complexity of biotherapeutic molecules is likely to lead to complex material properties of crystals in the solid state and to complex transitions. This complexity is explored using batch crystallised lysozyme as a model. The effects of drying and milling on the solid-state transformations of lysozyme crystals were monitored using differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), FT-Raman, and enzymatic assay. XRPD was used to characterise crystallinity and these data supported those of crystalline lysozyme which gave a distinctive DSC thermogram. The apparent denaturation temperature (Tm) of the amorphous lysozyme was ∼201 °C, while the Tm of the crystalline form was ∼187 °C. Raman spectra supported a more α-helix rich structure of crystalline lysozyme. This structure is consistent with reduced cooperative unit sizes compared to the amorphous lysozyme and is consistent with a reduction in the Tm of the crystalline form. Evidence was obtained that milling also induced denaturation in the solid-state, with the denatured lysozyme showing no thermal transition. The denaturation of the crystalline lysozyme occurred mainly through its amorphous form. Interestingly, the mechanical denaturation of lysozyme did not affect its biological activity on dissolution. Lysozyme crystals on drying did not become amorphous, while milling-time played a crucial role in the crystalline-amorphous-denatured transformations of lysozyme crystals. DSC is shown to be a key tool to monitor quantitatively these transformations.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1016/j.jpba.2015.05.011en_US
dc.subjectCrystalline-amorphous-denatured transformations; Differential scanning calorimetry; FT-Raman; Lysozyme crystals; Milling; X-ray powder diffractionen_US
dc.titleMapping the solid-state properties of crystalline lysozyme during pharmaceutical unit-operationsen_US
dc.status.refereedyesen_US
dc.date.Accepted2015-05-13
dc.typeArticleen_US
dc.type.versionNo full-text available in the repositoryen_US


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