The dissolution properties and physico-chemical properties of polymorphic forms of (.ALPHA.-bromoisovaleryl)urea.

Abstract

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, ΔHsol and ΔHdiss, 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 (ΔHtrans), differences of free energy at 37°C (ΔGT), differences of entropy at 37°C (ΔST), and entropy changes at transition temperatures (ΔStrans). The differences of free energy, which may affect the bioavaliabilities of polymorphs, and the ΔStrans values were found to be fairly small.