Investigating the solubility of deferiprone for preparation of its oral liquid formulation

Abstract

Introduction: Solubility is one of important physico-chemical properties of a drug in process of discovery and development. Cosolvency is one way of increasing solubility of drug between other methods. The solubility of deferiprone (DFP) has not been evaluated in the literature. Aim: Measurement of DFP solubility in binary solvents and provide predictive models for solubility of DFP in the investigated solvent systems. Methods: The solubility of deferiprone (DFP) in water, ethanol (EtOH), N-methyl-2-pyrrolidone (NMP), ethylene glycol (EG), propylene glycol (PG) and polyethylene glycol 400 (PEG 400) at 293.2, 298.2, 303.2, 308.2 and 313.2 K is reported and mathematically represented by van’t Hoff equation. The solubility of DFP in aqueous binary mixtures of EtOH, NMP, EG, PG, PEG 400 and glycerin and also the solubility of DFP in binary mixtures of EG with EtOH, NMP, PG and PEG 400 at 298.2 K is determined by using the shake flask method and the generated data is used to train the Jouyban-Acree model. Results: The solubility of DFP in water is increased by addition of the cosolvents and reached to the maximum values and decreased with further addition of the cosolvents but it is decreased in EG mixtures by addition of the cosolvents. The mean percentage deviations of the back-calculated solubilities against the corresponding experimental values were 1.5% and 2.1%, respectively for the mono- and mixed solvent systems. Conclusion: Based on the generated data, trained versions of the van’t Hoff and Jouyban-Acree models and their combination are presented for simulation of the variations of DFP solubility. These simulated data is in demand in the pharmaceutical industry for designing crystallization procedures and also formulation of liquid dosage forms of poorly soluble drugs.