Determination of the Mesalazine Solubility at Biorelevant Temperature

Abstract

Physicochemical properties of drug/drug candidates are still key inputs for drug discovery and development studies. The most important physicochemical properties of these substances are lipophilicity, solubility, acid/base character, permeability, and bio-accessibility. Among them, the knowledge about solubility is a crucial physicochemical property of drugs and is of high demand both in industry and academia. The aims of the current study are: to determine the solubility of mesalazine in the non-aqueous propylene glycol (PG) + 2-propanol and aqueous 1,4-dioxane binary mixtures at biorelevant temperature (310.2 K) by using co-solvency method, to perform density analysis in non-aqueous and aqueous binary mixtures for saturated systems, to characterize mesalazine equilibrated in the saturated solutions by XRD analyses. In this research, the solubility values of mesalazine were determined in the non-aqueous (propylene glycol (PG) + 2-propanol) and aqueous (1,4-dioxane + water) binary mixtures at biorelevant temperature (310.2 K) using the common shake-flask method. The experimental molar solubility (C_M) of mesalazine values in the diluted solutions was determined in the PG + 2-propanol and 1,4-dioxane + water binary mixtures using a plotted calibration curve (R² = 0.999) at 310.2 K. The maximum solubility in the molarity scale was obtained in neat PG (C_M = 1.03  ×  10^– 2 mol/L), and the minimum solubility in the neat 2-propanol (C_M = 5.14  ×  10^–4 mol/L) in non-aqueous binary mixtures. The maximum solubility value was obtained in 0.4 mass fraction (C_M = 1.68 ×  10^–2 mol/L) of 1,4-dioxane + water and the minimum solubility was obtained in neat 1,4-dioxane (C_M = 3.34 × 10^–3 mol/L) at 310.2 K. Density data were also determined and correlated with Jouyban–Acree model for saturated systems in non-aqueous and aqueous binary mixtures. The characterization tests of mesalazine equilibrated in saturated solutions were performed by X-ray diffraction (XRD) analyses from 10° to 70°. XRD analysis showed that the crystallinity of mesalazine remained unchanged and did not show any polymorphic transformation during the drug dissolution in the investigated binary mixture. Up to now, no data was reported for mesalazine solubility in these binary mixtures at biorelevant temperature.