Solubility of Sulfamerazine in Acetonitrile + Ethanol Cosolvent Mixtures: Thermodynamics and Modeling

Abstract

Sulfamerazine (SMR) is a drug used as an antibacterial agent in the treatment of some pathologies, such as bronchitis, prostatitis and urinary tract infections. Although this drug was developed in 1945 and, due to its toxicity, was partially displaced by penicillin, due to the current problem of bacterial resistance, compounds such as SMR have regained validity. In this context, the thermodynamic study of SMR in cosolvent mixtures of acetonitrile (MeCN) + ethanol (EtOH) at nine temperatures (278.15-318.15 K) is presented. The solubility of SMR was determined by UV-Vis spectrophotometry, following the guidelines of the shake-flask method. The solubility process was endothermic in all cases; thus, the minimum solubility was reached in pure EtOH at 278.15 K, and the maximum solubility was reached in pure MeCN at 318.15 K. Both the solution process and the mixing process were entropy-driven. On the other hand, the solubility data were modeled by using the van't Hoff-Yalkowsky-Roseman model, obtaining an overall average relative deviation of 3.9%. In general terms, it can be concluded that the solution process of SMR in {MeCN (1) + EtOH (2)} mixtures is thermodependent, favored by the entropy of the solution and mixture; additionally, the van't Hoff-Yalkowsky-Roseman model allows very good approximations to be obtained and is a simple model that starts from only four experimental data.

Keywords: Yalkowsky–Roseman; binary mixtures; infections; shake-flask method; solubility; sulfamerazine; thermodynamic properties; van’t Hoff.

Figure 6

Diagram of hypothetical mixing process (solution formation) [43].

Figure 1

Molecular structure of sulfamerazine [5].

Figure 2

Solubility of SMR (3) ($x_3$) as function of mass fraction of MeCN in {MeCN (1) + EtOH (2)} mixtures at different temperatures. •: 278.15 K; ∘: 283.15 K; ▲: 288.15 K; ∆: 293.15 K; ■: 298.15 K; □: 303.15 K; ⧫: 308.15 K; ◊: 313.15 K; ✶: 318.15 K.

Figure 3

Solubility of SMR (3) ($x_3$) as function of $\alpha$-scale of solvent HBD acidities.

Figure 4

DSC thermograms of SMR.

Figure 5

van’t Hoff plot of the mole fraction solubility of SMR ($x_3$) in different {MeCN (1) + EtOH (1)} mixture compositions. ∘: neat EtOH; ✶: $w_{0.1}$; ∆: $w_{0.2}$; ▲: $w_{0.3}$; ☐: $w_{0.4}$; x: $w_{0.5}$; ◊: $w_{0.6}$; ⧫: $w_{0.7}$; ⊗: $w_{0.8}$; ■: $w_{0.9}$; ●: neat MeCN.

Figure 7

Enthalpy–entropy compensation plot for solubility of SMR (3) in MeCN (1) + EtOH (2) mixtures at $T_{\mathrm{hm}}$ = 297.6 K.

Figure 8

Experimental solubility data versus predicted solubility data for 189 studied solubility data points of SMR in {MeCN (1) + EeOH (2)} mixtures.