Experimental Determination and Theoretical Calculation of the Eutectic Composition of Cefuroxime Axetil Diastereomers

Abstract

Cefuroxime axetil (CFA), an ester prodrug of cefuroxime exists as a pair of diastereoemers, namely isomer A and isomer B. To enable phase diagram construction, crystallization of the diastereomers of CFA from the commercially available amorphous drug substance was carried out. Isomer A was separated with a purity approaching 100% whereas the maximum purity of isomer B was 85% as confirmed by solution state proton NMR spectroscopy. The crystalline forms of isomer A and isomer B were confirmed as forms AI and BI, respectively, based on differential scanning calorimetry (DSC) analysis and powder X-ray diffraction. DSC analysis was used to observe the melting behavior of different diastereomer mixture compositions. The binary solid-liquid phase diagram for mixture compositions ranging from 0 to 85% w/w isomer B indicated the formation of a eutectic mixture having a melting temperature of 124.7 ± 0.4°C and a composition of 75% w/w (+/-5% wt.) isomer B. The eutectic composition was calculated using an index based on the van't Hoff equation for melting point depression and was found to be 75% isomer B and 25% isomer A. As CFA is present in commercial preparations as a mixture of diastereomers, the formation of a eutectic mixture between the diastereomers may impact the solubility and stability of the commercial product. Eutectic formation can be explained on the basis of the chemical similarity of diastereomers that favor miscibility in the liquid state.

Preparation and Characterization of a Eutectic Mixture of Fenofibric Acid and Nicotinic Acid and Evaluatuion of In Vivo Antihyperlipidemic Activity

“…DSC can be used to con rm the purity of the solid phase. When the melting point is lower than that of either of the components, DSC can identify the eutectic properties of multicomponent systems (Dalal et al, 2017). DSC thermograms of FA, NA, and the eutectic mixture of FA and NA in a 1:1 molar ratio are shown in Figure 2.…”

Dissolution Rate Enhancement and Physicochemical Characterization of a Fenofibric Acid–Nicotinamide Eutectic Mixture

“…The lowest melting point (TE) on the curve was defined as the eutectic temperature. 17 PXRD analysis was conducted to verify the formation of the FA-NIC eutectic mixture at a 0.3:0.7 molar ratio. The PXRD patterns of FA, NIC, and the FA-NIC eutectic mixture are shown in Figure 4.…”

Determination of the imatinib mesylate purity by differential scanning calorimetry

“…Poza wyznaczaniem czystości stosowana jest m.in. do badania zjawiska polimorfizmu, stabilności leków, interakcji leków z substancjami pomocniczymi, przejść fazowych, rozkładu, a także przepuszczalności błon biologicznych dla leków [10][11][12][13][14][15].…”