Dissolution improvement and solubility enhancement of two tumor-associated enzyme inhibitors via the formation of eutectic mixtures.

Eutectic mixtures have emerged as an effective means to improve the physicochemical properties of drugs for clinical applications. In this study, two tumor-associated enzyme inhibitors based eutectic mixtures, i.e., Imatinib (IMA) with Adenine Phosphate (AdPh) (IMA-AdPh EUT) and Olaparib (OLA) with AdPh (OLA-AdPh EUT), were designed and prepared via liquid-assisted grinding method. The binary phase diagrams, constructed from differential scanning calorimetry (DSC) results, demonstrated that the optimal molar ratios of IMA in IMA-AdPh EUT and OLA in OLA-AdPh EUT were 1:1 and 3:2, respectively. The eutectic mixtures were further verified by powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR). Equilibrium solubility studies and powder dissolution tests demonstrated that IMA or OLA in either eutectic mixture exhibited enhanced solubility and superior dissolution performance comparing to as single component or in the physical mixture. Consequently, IMA-AdPh EUT and OLA-AdPh EUT may provide a promising formulation strategy to improve solubility and dissolution performance of tumor-associated enzyme inhibitors.