Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid
dc.contributor.author | Paluch, Krzysztof J. | * |
dc.contributor.author | McCabe, T. | * |
dc.contributor.author | Müller-Bunz, B. | * |
dc.contributor.author | Corrigan, O.I. | * |
dc.contributor.author | Healy, A.M. | * |
dc.contributor.author | Tajber, L. | * |
dc.date.accessioned | 2018-01-03T14:23:31Z | |
dc.date.available | 2018-01-03T14:23:31Z | |
dc.date.issued | 2013-08 | |
dc.identifier.citation | Paluch 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.uri | http://hdl.handle.net/10454/14341 | |
dc.description | Yes | en_US |
dc.description.abstract | Multi-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.sponsorship | Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/ B1158. | en_US |
dc.language.iso | en | en_US |
dc.relation.isreferencedby | http://dx.doi.org/10.1021/mp400127r | en_US |
dc.rights | This 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/mp400127r | en_US |
dc.subject | Ciprofloxacin; Succinic acid; Solubility; Ternary phase diagram; Single crystal X-ray; Dynamic vapor sorption; Morphology | en_US |
dc.title | Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid | en_US |
dc.status.refereed | Yes | en_US |
dc.date.Accepted | 2013-08-15 | |
dc.date.application | 2013-08-15 | |
dc.type | Article | en_US |
dc.type.version | Accepted Manuscript | en_US |
refterms.dateFOA | 2018-07-29T03:28:04Z |