Thermodynamic Characteristics of Phenacetin in Solid State and Saturated Solutions in Several Neat and Binary Solvents

Abstract

The thermodynamic properties of phenacetin in solid state and in saturated conditions in neat and binary solvents were characterized based on differential scanning calorimetry and spectroscopic solubility measurements. The temperature-related heat capacity values measured for both the solid and melt states were provided and used for precise determination of the values for ideal solubility, fusion thermodynamic functions, and activity coefficients in the studied solutions. Factors affecting the accuracy of these values were discussed in terms of various models of specific heat capacity difference for phenacetin in crystal and super-cooled liquid states. It was concluded that different properties have varying sensitivity in relation to the accuracy of heat capacity values. The values of temperature-related excess solubility in aqueous binary mixtures were interpreted using the Jouyban–Acree solubility equation for aqueous binary mixtures of methanol, DMSO, DMF, 1,4-dioxane, and acetonitrile. All binary solvent systems studied exhibited strong positive non-ideal deviations from an algebraic rule of mixing. Additionally, an interesting co-solvency phenomenon was observed with phenacetin solubility in aqueous mixtures with acetonitrile or 1,4-dioxane. The remaining three solvents acted as strong co-solvents.

Experimental and Theoretical Screening for Green Solvents Improving Sulfamethizole Solubility

“…The solubility measurements were performed based on the shake-flask procedure reported in our previous papers [11][12][13]15]. First, the mixtures containing SMT solution and undissolved excess of solid were prepared in glass test tubes.…”

“…This behavior is quite common, and it is manifested by the appearance of a maximum on the molar fraction solubility plotted as a function of binary solvent composition. Some recent examples reported in the literature of such behavior include aqueous binary mixtures of nicotinamide in dimethyl sulfoxide (DMSO) [11], theophylline in 1-butanol [12], phenacetin in 1,4-dioxane [13,14], sulfanilamide in 1,4-dioxane [15], paracetamol in ethanol and propylene glycol [16], 4-(hydroxymethyl)benzoic acid in ethanol [17], and piroxicam in ethanol [18].…”

New Screening Protocol for Effective Green Solvents Selection of Benzamide, Salicylamide and Ethenzamide

“…Due to the absence of corresponding experimental data for benzamide, these two solvents were chosen as the first choice for further experimental investigations and to expand the pool of available solubility data. These two solvents are characterized by high efficiency in dissolving many solids, including active pharmaceutical ingredients [ 18 , 40 , 45 , 47 , 49 , 111 , 112 ]. Their solubilizing potential can be interpreted in terms of solute-solvent affinity and in the particular case of benzamide the expected structures and corresponding energetics, determined theoretically, are documented in Figure 1 .…”

“…Noteworthy, although water is often considered an anti-solvent compared to organic solvents, in some cases, it can enhance the solubility, as a result of a significant co-solvation effect. Such synergism was frequently observed in many aqueous binary mixtures as for example for sulfamethizole in 1,4-dioxane [ 40 , 44 ] or acetonitrile binary mixtures [ 40 ], sulfanilamide in ethanol, acetonitrile and 1,4-dioxane [ 45 , 46 ], nicotinamide in DMSO and acetonitrile [ 18 ], phenacetin in 1,4-dioxane [ 47 , 48 ], amoxicillin in DMF-water [ 49 ] and theophylline in aqueous DMF, DMSO, 1,4-dioxane, 1-propanol and 1-butanol [ 33 , 50 , 51 ].…”

“…Firstly, the pool of experimental solubility data is extended by providing new results obtained for titled compounds in two proton accepting organic solvents (DMSO and DMF) and their aqueous mixtures. The choice of DMSO and DMF was mainly guided by previous research showing their high efficiency in the case of other amides and sulfonamides [ 18 , 40 , 45 , 47 ]. Secondly, the accuracies of solubility computed using the COSMO-RS methodology were carefully checked against available experimental data of benzamide, salicylamide, and ethenzamide.…”