Eutectic Mixtures to Enhance the Solubility of Active Pharmaceutical Ingredients: Density Functional Theory and Infrared Spectroscopy Approaches

The major issue with active pharmaceutical ingredients (APIs) is their slow dissolution rate and solubility. This makes them less likely to get into the body and less bioavailable. About 40 % of the drugs already on the market and 90 % being made have APIs that do not dissolve well in water. To deal with this problem, authors have designed eutectic mixture (EMs) of different drugs (danazol, griseofulvin, mefenamic acid, tolfenamic acid and tadalafil) with zinc chloride; studied their interaction and thermodynamic parameters using Density Functional Theory (DFT) computation. DFT calculations confirm an increase in the dipole moment of their EMs in comparison of APIs alone which increases the solubility. The change in Gibbs free energy of formation of EMs in the gaseous phase shows their feasibility ans stability. Eutectic mixtures of various drugs with zinc chloride have been designed and investigated by DFT calculations. Dipole moment of eutectic mixtures is higher than that of APIs alone, indicate enhancement in solubility as well as the value of ΔG indicated the feasibility for the formation of eutectic mixtures.