Solution Thermodynamics of Isoniazid in PEG 400 + Water Cosolvent Mixtures

Solubility studies are an essential requirement for the development of more efficient industrial processes. In this context, the use of cosolvents is a relevant strategy in pharmaceutical sciences, especially when dealing with green solvents such as water (W (2)) and Polyethylene glycol 400 (PEG 400 (1)). The objective of this study is to thermodynamically analyze the solubility of isoniazid in {PEG 400 (1) + W (2)} cosolvent mixtures at seven temperatures (288.15 to 318.15 K). The study was conducted by calculating thermodynamic functions from experimental solubility data determined using the flask shaking method, employing UV spectrophotometry as the quantification technique. The dissolution process was shown to be endothermic and entropy-driven. Although maximum solubility would be expected to be achieved in a cosolvent mixture, given that the solubility parameter of isoniazid (30.54 MPa1/2) has an intermediate value between the two pure solvents (PEG 400 ≈ 22.5 MPa1/2; Water ≈47.8 MPa1/2), maximum solubility is achieved in pure PEG 400 and the lowest solubility is achieved in pure water.