Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid
Item Type:Journal Article
Citation:Paluch KJ, McCabe T, Müller-Bunz H, Corrigan OI, Healy AM, Tajber L, Formation and physicochemical properties of crystalline and amorphous salts with different stoichiometries formed between ciprofloxacin and succinic acid, Molecular pharmaceutics, 10, 10, 2013, 3640-54
Ciprofloxacin salts_MS.pdf (Accepted for publication (author's copy) - Peer Reviewed) 2.238Mb
Multi-ionisable compounds, such as dicarboxylic acids, offer the possibility of forming salts of drugs with multiple stoichiometries. Attempts to crystallise 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 non-congruently 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 hour 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.
Type of material:Journal Article
Series/Report no:Molecular pharmaceutics
Availability:Full text available