Thermodynamic Properties of Form A and Form B of Florfenicol

Abstract

In this research, a new polymorph of florfenicol (form B) was discovered and successfully prepared. The new polymorph was characterized and identified by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) techniques. It was found that form A has lower melting temperature while higher fusion enthalpy. The solubility of both florfenicol polymorphs in methanol, 2-propanol, acetone, acetonitrile, ethanol, and ethyl acetate were experimentally determined from 278.15 to 318.15 K with a dynamic method. For all tested solvents, the solubility data of florfenicol form B are higher than those of form A. The modified Apelblat model, the NRTL model, and the λh model were adopted to calculate the solubility of florfenicol two forms with satisfactory correlation results. In addition, the dissolution thermodynamic properties of florfenicol form A and form B, including dissolution enthalpy, dissolution entropy, and Gibb's dissolution energy in all tested solvents, were obtained. Combining the results of DCS determination, the solubility, and all the dissolution thermodynamic data, it was confirmed that florfenicol polymorph A and polymorph B belong to the enantiotropic polymorph system.

Measurement and Correlation of the Solubility of Florfenicol Form A in Several Pure and Binary Solvents

“…The DSC and XRPD data of form A have been reported before . The melting properties of florfenicol in this work were determined by DSC (differential scanning calorimetry, TA Instruments, Q2000) under a nitrogen atmosphere (50.0 cm 3 ·min –1 ).…”

In situ Formed Implants, Based on PLGA and Eudragit Blends, for Novel Florfenicol Controlled Release Formulations

“…Principal FF signals are observed at 8.10, 16.21 y 26.85 . 42 When EuE100 is added to the formulations (Fig. 7a), the FF signals are less perceptible.…”

“…Differential Scanning Calorimetry (DSC) results for selected formulations are shown in Supplementary material (Figure SM3) . FF fusion peak can be observed at 152 C. 42,46 The glass transition temperature of PLGA is 37e38 C. 47 The formulation P50 presents a fusion peak at 155 C and can be associated with crystalline FF. The difference with pure FF is possibly related to interactions with the polymeric matrix.…”

Thermodynamic vs. Kinetic Basis for Polymorph Selection

“…A regular experimental finding for polymorph pairs of organic compounds is that high supersaturations seem to favour the initial formation and in some circumstances the persistence of the metastable form. Polymorphs pairs Eflucimibe [12], d-Mannitol [28] and Famotidine [30], o-Aminobenzoic acid, Stavudine [31], L-Histidine [32], BPT Propyl Ester [33], Florfenicol [34] and L-Glutamic acid [35] each of which show a preference for the stable polymorph at low supersaturations and a preference for the metastable polymorph at higher supersaturations. Shiau used a competitive kinetic model that predicted this behaviour for eflucimibe based on the model derived association and dissociation rate constant for the two polymorphs [36].…”