Solubility and thermodynamic function of a bioactive compound bergenin in various pharmaceutically acceptable neat solvents at different temperatures

Abstract

Bergenin is neither a highly lipophilic nor a highly hydrophilic bioactive compound due to which its dissolution and permeation are poor which results in poor oral bioavailability. The solubility data of bergenin are scarce in literature. Therefore, in this study, the solubility of bergenin was determined in eleven different pharmaceutically acceptable neat solvents namely water, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), 1-butanol, 2-butanol, ethyl acetate (EA), dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Transcutol at five different temperatures (T=298.15K–318.15K) and atmospheric pressure (p=0.1MPa). Experimental solubility expressed in mole fraction of bergenin was correlated with semi-empirical models. Root mean square deviations were recorded <1% for the Apelblat model and <2% for the van’t Hoff model. The mole fraction solubility of bergenin was recorded highest in PEG-400 (4.15×10−2 at T=318.15K) followed by DMSO (2.30×10−2 at T=318.15K), Transcutol (2.28×10−2 at T=318.15K), PG (1.19×10−2 at T=318.15K), EG (1.17×10−2 at T=318.15K), ethanol (7.77×10−3 at T=318.15K), IPA (1.69×10−3 at T=318.15K), EA (6.71×10−4 at T=318.15K), 2-butanol (5.14×10−4 at T=318.15K), 1-butanol (4.92×10−4 at T=318.15K) and water (1.87×10−4 at T=318.15K). The results of apparent thermodynamic analysis in terms of standard enthalpy indicated that the dissolution of bergenin is endothermic in all pharmaceutically acceptable neat solvents. The solubility results of this study could be useful in purification, recrystallization and formulation development of bergenin.