Liquid pharmaceuticals formulation by eutectic formation

• DOI: 10.1016/j.fluid.2017.05.009
• Publication Date: 2017-05-08T02:30:56Z
• Authors: Andrew P. Abbott; Essa I. Ahmed; Kamalesh Prasad; Idrees B. Qader; Karl S. Ryder
• Keywords: Deep eutectic solvent; Hydrogen bonding; Technology; Science & Technology; MIXTURES; Chemical; 02 engineering and technology; 540; Chemistry; Engineering; Formulation; IONIC LIQUIDS; SYSTEMS; Physical Sciences; Physical; Thermodynamics; Polymorphism; DRUG; SOLVENTS; 0210 nano-technology

Abstract The amphiphilic nature of many pharmaceutical active ingredients often makes them difficult to solubilise and leads to significant wastage through non-optimal dosage. In this study it is shown that highly concentrated liquid formulations can be produced from pharmaceutical active ingredients which either contain a strong hydrogen bonding functionality e.g. -OH or -COOH or a quaternary ammonium moiety. These mixtures can overcome solubility issues in water as the eutectics prevent recrystallization of the active ingredient when dispersed in water. The depression of freezing point for these eutectic mixtures is modelled using the enthalpy of hydrogen bond formation which was calculated using calorimetric data. The study also demonstrates that complex drug molecules which exhibit polymorphism such as Adiphenine and Ranitidine can be formulated into a homogeneous liquid and the hydrogen bond donor can also be a pharmaceutical active ingredient e.g. aspirin.