Zaltoprofen/4,4'-Bipyridine: A Case Study to Demonstrate the Potential of Differential Scanning Calorimetry (DSC) in the Pharmaceutical Field

Abstract

The Zaltoprofen/4,4'-Bipyridine system gives rise to two co-crystals of different compositions both endowed - in water and in buffer solution at pH 4.5 - with considerably higher solubility and dissolution rate than the pure drug. The qualitative and quantitative analysis of the DSC measurements, carried out on samples made up of mixtures prepared according to different methodologies, allows us to elaborate and propose an accurate thermodynamic model that fully takes into account the qualitative aspects of the complex experimental framework and which provides quantitative predictions (reaction enthalpies and compositions of the co-crystals) in excellent agreement with the experimental results. Co-crystal formation and cocrystal compositions were confirmed by X-ray diffraction measurements as well as by FT-IR and NMR spectroscopy measurements. The quantitative processing of DSC measurements rationalizes and deepens the scientific aspects underlying the so-called Tammann's triangle and constitutes a model of general validity. The work shows that DSC has enormous potential, which however can be fully exploited only by paying adequate attention to the experimental aspects and the quantitative processing of the measurements.

Keywords: Cocrystals; Differential scanning calorimetry; Dissolution rate; Solubility; Spectroscopic characterization; Thermodynamic model; Zaltoprofen/4,4' Bipyridine.