Yes / 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. / Solid State Pharmaceutical Cluster (SSPC), supported by Science Foundation Ireland under grant number 07/SRC/ B1158.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/14341 |
| Date | 15 August 2013 |
| Creators | Paluch, Krzysztof J., McCabe, T., Müller-Bunz, B., Corrigan, O.I., Healy, A.M., Tajber, L. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| 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, Unspecified |
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