The dissolution behavior and thermodynamic properties of amlodipine in mixtures of n-propanol/isopropanol + water

Abstract

Improving the solubility of poorly water-soluble drugs is one of the biggest problems. In this study, the dissolution behavior of amlodipine in aqueous mixtures of co-solvents including n-propanol and isopropanol within the temperature range from 273.15 K to 313.15 K was investigated and presented by Jouyban-Acree model. In n-propanol (1) + water (2) binary mixtures, the maximum mole fraction solubility of amlodipine (3.546 × 10-2) was observed at 313.15 K when the mass fraction of n-propanol was 0.80. The corresponding data (2.714 × 10-2) for isopropanol (1) + water (2) systems was obtained with the mass fraction of 0.60 for isopropanol at 313.15 K. The maximum data for water was (2.245 × 10-5) at 313.15 K, an about 1.580 × 103 fold increase in n-propanol + water binary mixtures, and 1.209 × 103 fold increase in isopropanol + water systems. The co-solvency behavior of amlodipine in two aqueous solutions was analyzed by acidic partial solubility parameter (δ1a), basic partial solubility parameter (δ1b) and Hildebrand solubility parameter (δ1). The positive coefficient of δ1 and δ1a related to favorable nonspecific and specific interactions, respectively. Moreover, amlodipine behaves as Lewis base toward n-propanol + water and isopropanol + water binary mixtures. Besides, the outcomes of the “apparent thermodynamic analysis” showed that the dissolution of amlodipine was endothermic and entropy-driven in all composition of n-propanol + water and isopropanol + water binary mixtures.