Thermodynamic modelling of solubility and preferential solvation for ribavirin (II) in co-solvent mixtures of (methanol, n -propanol, acetonitrile or 1,4-dioxane) + water

Abstract

a b s t r a c tThe equilibrium solubility of ribavirin in solvent mixtures of {methanol (1) + water (2)}, {n-propanol (1) + water (2)}, {acetonitrile (1) + water (2)} and {1,4-dioxane (1) + water (2)} was determined experimentally by using isothermal dissolution equilibrium method within the temperature range from (278.15 to 318.15) K under atmospheric pressure (101.1 kPa). At the same temperature and mass fraction of methanol (n-propanol, acetonitrile or 1,4-dioxane), the mole fraction solubility of ribavirin is greater in (methanol + water) than in the other three solvent mixtures. The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood-Buff integrals. The preferential solvation parameters for methanol, n-propanol, acetonitrile or 1,4-dioxane (dx 1,3 ) were negative in the four solvent mixtures with a very wide compositions, which indicated that ribavirin was preferentially solvated by water. Temperature had little effect on the preferential solvation magnitudes. The higher solvation by water could be explained in terms of the higher acidic behaviour of water interacting with the Lewis basic groups of the ribavirin. Besides, the solubility of the drugs was mathematically represented by using the Jouyban-Acree model, van't Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 1.57% for correlative studies. It is noteworthy that the solubility data presented in this work contribute to expansion of the physicochemical information about the solubility of drugs in binary solvent mixtures and also allows the thermodynamic analysis of the respective dissolution and specific solvation process.

Cyclodextrins in the antiviral therapy

“…Characteristic examples are ribavirin [100], which has 14.2%, >10%, 0.33%, and imiquimod [101] with ≈2.5%, ≈0.6% on the homepage of a known chemical database. In technical papers, 7.9% for ribavirin [102] and 0.24% for imiquimod [56] are reported.…”

Measurement and Correlation of the Solubility and Thermodynamic Properties of Ribavirin(II) in Nine Pure Solvents and (1-Propanol + Water) Binary Solvents

“…This drug has four different crystal forms, with form II as the most prevalent. 5 Ribavirin(II) has a definite curative effect and low side effects and has been widely used in the treatment of various diseases caused by DNA and RNA viruses, such as respiratory tract infections, viral pneumonia, B encephalitis, and hepatitis C. The final operation is usually recrystallized by cooling to obtain refined products of ribavirin(II). 6 The thermodynamic properties of ribavirin(II) are important for its industrial production and clinical treatment; 5 however, related research is relatively insufficient.…”

“…36791-04-5) is a new type of synthetic nucleoside broad-spectrum antiviral drug, and its molecular structure is shown in Figure . This drug has four different crystal forms, with form II as the most prevalent . Ribavirin­(II) has a definite curative effect and low side effects and has been widely used in the treatment of various diseases caused by DNA and RNA viruses, such as respiratory tract infections, viral pneumonia, B encephalitis, and hepatitis C. The final operation is usually recrystallized by cooling to obtain refined products of ribavirin­(II) .…”

Solubility of 5-Fluorocytosine in Different Pure and Binary Mixed Solvents: Measurement, Model Correlation, Solvent Effect, and Preferential Solvation

“…Even one crystal form of the same drug has a therapeutic effect, and the other will produce a side effect. As known to all, solubility plays an important role in pharmaceutical science and industry . The knowledge of solubility in different solvents provides a reference for the optimization of crystal forms and the development of dosage forms to solve the problems of low bioavailability and medical solutions .…”

“…As known to all, solubility plays an important role in pharmaceutical science and industry. 13 The knowledge of solubility in different solvents provides a reference for the optimization of crystal forms and the development of dosage forms to solve the problems of low bioavailability and medical solutions. 14 In addition, solubility is crucial for drug production and crystallization for the purification process.…”