The Dissolution Properties and Physico-chemical Properties of Polymorphic Forms of (α-Bromoisovaleryl) urea

抄録

The dissolution properties and physico-chemical properties of three polymorphic forms of (α-bromoisovaleryl) urea are reported. Form II transformed to form I repidly in water at 37°C, but this transition was delayed by 0.25% gelatin. The solubility of form II was 50% higher than that form I. The transition temperatures of form II to form I, and form III to form I were 70.2°C and 11.4°C, respectively, as determined by measurements of dissolution rates and solubilities. The enthalpy values, ΔH_sol and ΔH_diss, of the polymorphs were calculated. The thermodynamic values of form II and form III for the conversion to form I were calculated from these values, i.e. heats of transition (ΔH_trans), differences of free energy at 37°C (ΔG_T), differences of entropy at 37°C (ΔS_T), and entropy changes at transition temperatures (ΔS_trans). The differences of free energy, which may affect the bioavaliabilities of polymorphs, and the ΔS_trans values were found to be fairly small.