Thermodynamic Assessment of Triclocarban Dissolution Process in N-Methyl-2-pyrrolidone + Water Cosolvent Mixtures

Abstract

Solubility is one of the most important physicochemical properties due to its involvement in physiological (bioavailability), industrial (design) and environmental (biotoxicity) processes, and in this regard, cosolvency is one of the best strategies to increase the solubility of poorly soluble drugs in aqueous systems. Thus, the aim of this research is to thermodynamically evaluate the dissolution process of triclocarban (TCC) in cosolvent mixtures of {N-methyl-2-pyrrolidone (NMP) + water (W)} at seven temperatures (288.15, 293.15, 298.15, 303.15, 308.15, 313.15 and 318.15 K). Solubility is determined by UV/vis spectrophotometry using the flask-shaking method. The dissolution process of the TCC is endothermic and strongly dependent on the cosolvent composition, achieving the minimum solubility in pure water and the maximum solubility in NMP. The activity coefficient decreases from pure water to NMP, reaching values less than one, demonstrating the excellent positive cosolvent effect of NMP, which is corroborated by the negative values of the Gibbs energy of transfer. In general terms, the dissolution process is endothermic, and the increase in TCC solubility may be due to the affinity of TCC with NMP, in addition to the water de-structuring capacity of NMP generating a higher number of free water molecules.

Keywords: N-methyl-2-pyrrolidone; cosolvent; modeling; simulation; solubility; thermodynamics; triclocarban; water.

Figure 1

Molecular structure of triclocarban.

Figure 2

Mole fraction of TCC (10${}^3$ $x_3$) depending on the mass fraction of NMP in the {NMP (1) + W (2)} mixtures free of TCC. •: 288.15 K; ∘: 293.15 K; △: 298.15 K; ▲: 303.15 K; ◻: 308.15 K; ◼: 313.15 K; 🟉: 318.15 K.

Figure 3

DSC thermograms of TCC.

Figure 4

Relation between enthalpy (${\mathsf{\Delta }}_{\mathrm{soln}}H°$) and entropy ($T_{\mathrm{hm}}{\mathsf{\Delta }}_{\mathrm{soln}}S°$) in terms of the process of TCC (3) solution in {NMP (1) + W (2)} cosolvent mixtures at 302.8 K. The isoenergetic curves for ${\mathsf{\Delta }}_{\mathrm{soln}}G°$ are represented by dotted lines.

Figure 5

Relation between enthalpy (${\mathsf{\Delta }}_{\mathrm{tr}}H°$) and entropy ($T_{\mathrm{hm}}{\mathsf{\Delta }}_{\mathrm{tr}}S°$) of the process transfer of TCC (3) in {NMP (1) + W (2)} cosolvent mixtures at 302.8 K. The isoenergetic curves for ${\mathsf{\Delta }}_{\mathrm{mix}}G°$ are represented by dotted lines.

Figure 6

Diagram of the hypothetical of solution process [71].

Figure 7

Relation between enthalpy (${\mathsf{\Delta }}_{\mathrm{mix}}H°$) and entropy ($T_{\mathrm{hm}}{\mathsf{\Delta }}_{\mathrm{mix}}S°$) of the process mixing of TCC (3) in {NMP (1) + W(2)} cosolvent mixtures at 302.8 K. The isoenergetic curves for ${\mathsf{\Delta }}_{\mathrm{mix}}G°$ are represented by dotted lines.

Figure 8

Enthalpy–entropy compensation plot for the solubility of TCC (3) in {NMP (1) + W (2)} mixtures at $T_{\mathrm{hm}}$ = 302.8 K.