STABILITY OF UREA IN SOLUTION AND PHARMACEUTICAL PREPARATIONS 195 at higher temperature and at pH values more than 8.0 and less than 4.0. Therefore, urea recovers in the range of pH 5.0–8.0, and the minimum possible temperature reduces the losses of product. In non-aqueous solvents, isopropanol showed the best effect in retard- ing the decomposition of urea. Within the experimental range of temperature and initial urea concentration values, the lowest urea degradation was performed with lactate buffer pH 6.0. REFERENCES (1) F. Wöhler, On the decomposition of urea and uric acid at high temperature. Ann. Phys. Chemie, 15, 619–630 (1829). (2) H. R. Shaw and D. G. Walker, Kinetic studies of thiourea derivatives. IV. The methylated thioureas. Conclusions. J. Am. Chem. Soc., 80, 5337–5342 (1958). (3) G. Estiu and K. M. Merz, The hydrolysis of urea and the profi ciency of urease. J. Am. Chem. Soc., 126, 6932–6944 (2004). (4) A. N. Alexandrova and A. W. Jorgensen, Why urea eliminates ammonia rather than hydrolyzes in aque- ous solution, J. Phys. Chem. B, 111, 720–730 (2007). (5) N. D. Jespersen, A thermochemical study of the hydrolysis of urea by urease. J. Am. Chem. Soc., 97, 1662–1667 (1975). (6) P. A. Karplus, M. A. Pearson, and R. P. Hausinger, 70 Years of crystalline urease: What have we learned? Acc. Chem. Res., 30, 330–337 (1997). (7) H. B. Bull, K. Bresse, G. L. Ferguson, and C. A. Swenson, The pH of urea solutions. Arch. Biochem. Biophys., 104, 297–304 (1964). (8) W. H. R. Shaw and J. J. Bordeaux, The decomposition of urea in aqueous media. J. Am. Chem. Soc., 77, 4729–4733 (1955). (9) R. C. Warner, The kinetics of the hydrolysis of urea and of arginine. J. Bio. Chem., 142, 705–723 (1942). (10) M. A. Schwartz and E. Nelson, Husa’s Pharmaceutical Dispensing. (Mack Publishing Co, London, 1996). (11) H. L. Welles, A. R. Giaquinto, and R. E. Lindstrom, Degradation of urea in concentrated aqueous solu- tion. J. Pharm. Sci., 60, 1212–1216 (1971). (12) W. R. Fearon, The carbamido diacetyl reaction: A test for citrulline. Biochem. J., 33, 902–907 (1939). (13) M. T. Knorst, R. Neubert, and W. Wohlrab, Analytical methods for measuring urea in pharmaceutical formulations. J. Pharm. Biomed. Anal., 15, 1627–1632 (1997). (14) Council of Europe, European Pharmacopoeia, 4th Ed. (European Council, Strasbourg, 2005).