Solubility and thermodynamics of 4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxybenzoyl)-3,4-dihydropyrimidin-2(1H)-one in various pure solvents at different temperatures

Abstract

Dihydropyrimidine derivatives have great potential in the treatment of various kinds of cancers. The main problem associated with these medicines is the poor solubility of these drugs in an aqueous media. Hence, in the current research work, the solubility of dihydropyrimidine derivative i.e. 4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxybenzoyl)-3,4-dihydropyrimidin-2(1H)-one [coded as DHP-5] was measured in twelve different pure solvents such as water, methanol, ethanol, 1-butanol, 2-butanol, isopropyl alcohol (IPA), ethylene glycol (EG), propylene glycol (PG), ethyl acetate (EA), dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Carbitol® at five different temperatures and atmospheric pressure. Experimental solubilities (expressed as mole fraction) of DHP-5 were fitted and correlated with Van't Hoff and Apelblat models. The solubilities (expressed as mole fraction) of DHP-5 at T=318.15K were observed highest in PEG-400 (1.21×10−2) followed by DMSO (9.96×10−3), Carbitol® (6.24×10−3), EA (3.45×10−3), 1-butanol (1.46×10−3), 2-butanol (1.45×10−3), PG (1.33×10−3), IPA (1.13×10−3), EG (1.07×10−3), ethanol (8.02×10−4), methanol (5.77×10−4) and water (2.54×10−5) and similar trend was observed at all five different temperatures investigated. Apparent thermodynamic analysis indicated that the dissolution behavior of DHP-5 was spontaneous, endothermic and entropy-driven in all pure solvents investigated.