Measurement and Thermodynamic Modeling of Oxaprozin Solubility in Polymers and Mixed Solutions

Abstract

Measuring and modeling the solubility of drugs in different solvent systems is helpful to guide the selection of appropriate solvents at various stages of drug formulation development. In this work, the gravimetrical method was used to determine the solubility data of oxaprozin (OXA) in different compositions of water/organic solvents (methanol and ethanol) binary mixtures within the range of 293.15 to 333.15 K. Subsequently, the differential scanning calorimetry method was used to measure the solubility of the drug in polymers (Polyethylene Glycol 6000 and Polyvinylpyrrolidone K30) at above 400 K. Then, the solubility of OXA in ultrapure water and polymer aqueous solution was acquired by UV spectrophotometry or HPLC within a temperature range of 303.15 to 323.15 K. Finally, the experimental values were compared with the calculated values from the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) to investigate the prediction accuracy of this model in different complex mixed solvent systems. The average relative deviations (ARD) were used to evaluate the model performance of PC-SAFT. Furthermore, PC-SAFT combined with solid−liquid equilibrium theory not only modeled the phase behavior between pure or mixed solvents and drugs independent of the molecular weight of the solvent but also did not require any experimental data or model parameters from the ternary system to predict the phase behavior of OXA in binary solvents. The results of this work illustrate that PC-SAFT is a beneficial model in drug development.

Solubility Measurement and Thermodynamic Modeling of Bifendate in 13 Pure Solvents at Temperatures from 293.15 to 333.15 K

“…The solubility data of the drug in 13 pure organic solvents (methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, isopropanol, methyl acetate, ethyl acetate, 1-propyl acetate, 1-butyl acetate, 1-pentyl acetate, acetonitrile, and acetone) at temperatures ranging from 293.15 to 333.15 K at atmospheric pressure were measured by the gravimetric method. Our previous work has demonstrated the accuracy of this measurement method . The error bars were so small that they were almost invisible in the graph.…”

“…This suggested that PC-SAFT had a good prediction of drug solubility in pure solvents. In addition, Wu et al determined the solubilities of oxaprozin in pure solvents and mixed solvents and predicted these phase equilibrium data by the PC-SAFT combining with solid–liquid equilibrium theory . However, oxaprozin has a hydrogen bond donor while bifendate has no hydrogen bond donors.…”

“…The black solid line shows that the experimental and calculated solubility data are exactly equal. The points represent the solubility of OXA in water (squares), organic solvents (circles), polymers (hexagons), water/polymer mixed solvents (triangles), and water/organic solvent mixed solvents (rhombuses), respectively . The pentagons represent the solubility of bifendate in organic solvents.…”

“…In addition, PC-SAFT has a wide range of applications in a variety of systems, such as ionic liquid, polymer, electrolyte solution and so on. Recently, we found that the great modeling and prediction performance of PC-SAFT for oxaprozin (OXA) in different molecular weights of pure solvent systems and aqueous binary solvents . However, bifendate and oxaprozin, both classified as BCS II drugs, , have different molecular structures.…”