Solubility and solution thermodynamics of nortriptyline hydrochloride in organic solvents: Experiment and correlation

The present study is focused on the determination of the equilibrium solubility of nortriptyline hydrochloride (NTT) (Form II) in 10 pure solvents essential for chemical and pharmaceutical industry: ethanol (EtOH), n-propanol (n-PrOH), n-butanol (n-BuOH), isopropanol (i-PrOH), acetonitrile (ACN), dimethyl formamide (DMF), acetone (Ace), methyl ethyl ketone (MEK), tetrahydrofuran (THF), n-octanol (n-OctOH). The solvents were selected on the principles of their different molecular structures, polarities and properties in order to provide the information useful for drug crystallization and purification. The experiments were carried from 288.15 K to 318.15( ± 0.1) K at 5 K intervals by the gravimetric and spectrophotometric methods. The following sequence of the solvents according to the values of NTT solubility at a standard temperature of 298.15 K was revealed: EtOH>n-PrOH≥n-BuOH>DMF>n-OctOH≥i-PrOH>THF>Ace>MEK>ACN. The influence of the solvent polarity on the solubility of NTT in comparison with the structurally similar drug amitryptiline hydrochloride from the literature sources was revealed. The results on the NTT experimental solubility were correlated by the thermodynamic models: van't Hoff equation, modified Apelblat equation, λh equation, two-suffix Margules model, Wilson model, and NRTL model. The apparent dissolution thermodynamic functions were calculated using the van’t Hoff equation. The mixing thermodynamic parameters were disclosed and discussed in relation to the driving forces of the processes.