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dc.contributor.authorPaluch, Krzysztof J.
dc.contributor.authorMcCabe, T.
dc.contributor.authorMüller-Bunz, B.
dc.contributor.authorCorrigan, O.I.
dc.contributor.authorHealy, A.M.
dc.contributor.authorTajber, L.
dc.date.accessioned2018-01-03T14:23:31Z
dc.date.available2018-01-03T14:23:31Z
dc.date.issued2013-08
dc.identifier.citationPaluch KJ, McCabe T, Müller-Bunz H et al (2013) Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid. Molecular Pharmaceutics. 10(10): 3640-3654.en_US
dc.identifier.urihttp://hdl.handle.net/10454/14341
dc.descriptionYesen_US
dc.description.abstractMulti-ionizable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallize ciprofloxacin, a poorly water-soluble, amphoteric molecule with succinic acid (S) resulted in isolation of ciprofloxacin hemisuccinate (1:1) trihydrate (CHS-I) and ciprofloxacin succinate (2:1) tetrahydrate (CS-I). Anhydrous ciprofloxacin hemisuccinate (CHS-II) and anhydrous ciprofloxacin succinate (CS-II) were also obtained. It was also possible to obtain stoichiometrically equivalent amorphous salt forms, CHS-III and CS-III, by spray drying and milling, respectively, of the drug and acid. Anhydrous CHS and CS had melting points at ∼215 and ∼228 °C, while the glass transition temperatures of CHS-III and CS-III were ∼101 and ∼79 °C, respectively. Dynamic solubility studies revealed the metastable nature of CS-I in aqueous media, resulting in a transformation of CS-I to a mix of CHS-I and ciprofloxacin 1:3.7 hydrate, consistent with the phase diagram. CS-III was observed to dissolve noncongruently leading to high and sustainable drug solution concentrations in water at 25 and 37 °C, with the ciprofloxacin concentration of 58.8 ± 1.18 mg/mL after 1 h of the experiment at 37 °C. This work shows that crystalline salts with multiple stoichiometries and amorphous salts have diverse pharmaceutically relevant properties, including molecular, solid state, and solubility characteristics.en_US
dc.description.sponsorshipSolid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/ B1158.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1021/mp400127ren_US
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © 2013 American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/mp400127ren_US
dc.subjectCiprofloxacin; Succinic acid; Solubility; Ternary phase diagram; Single crystal X-ray; Dynamic vapor sorption; Morphologyen_US
dc.titleFormation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic aciden_US
dc.status.refereedYesen_US
dc.date.Accepted2013-08-15
dc.date.application2013-08-15
dc.typeArticleen_US
dc.type.versionAccepted Manuscripten_US
refterms.dateFOA2018-07-29T03:28:04Z


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