Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences
Cefuroxime Axetil, Dissolution Rate Enhancement, Eutectics, Intrinsic Dissolution Rate, Soluble Complexes, Thermal Analysis
The objective of the first part of this work was to understand the solid-state and solution behavior of a cephalosporin antibiotic prodrug, cefuroxime axetil (CFA). CFA is present in commercial products as a mixture of diastereomers, which commonly form eutectic mixtures. A phase diagram was constructed utilizing differential scanning calorimetry. It was observed that the diastereomers formed a eutectic mixture with a composition of 75% isomer B and a melting temperature of 124.8±0.5 °C. Phase solubility studies on diastereomer mixtures of various compositions showed that the diastereomers interacted to form a complex in solution. This interaction resulted in a solubility increase upon use of certain diastereomer combinations over any individual diastereomer.
A second major objective of this project was to study the dissolution behavior of interactive mixtures containing CFA. Mechanically stable interactive mixtures were prepared utilizing the amorphous and crystalline forms of the drug with hydrophilic carrier particles. The dissolution rate of CFA was significantly higher from interactive mixtures compared to both physical mixtures and pure drug agglomerates. The enhancement in dissolution rate by interactive mixing was attributed to a decrease in fraction of agglomerated drug particles and agglomerate particle size. Both these factors produced an increase in effective surface area of drug available for interaction with the dissolution medium.
Dalal, N. (2015). Understanding the Solid State, Solubility and Dissolution Behavior of Cefuroxime Axetil Diastereomers in Interactive Mixture Formulations (Doctoral dissertation, Duquesne University). Retrieved from http://ddc.duq.edu/etd/72