DEGRADATION OF LOMUSTINE (CCNU) IN AQUEOUS-SOLUTIONS

The stability of lomustine in buffered aqueous solutions was investigated over the pH range 2.6-9.0. The degradation rate was unaffected by pH up to a pH of about 5 but increased at higher pH. The suggested unimolecular degradation mechanism in the pH-independent region of the pH-rate profile is supported by the activation parameters, the solvent isotope effect and other data obtained during this investigation. The effect of six cyclodextrin (CD) derivatives on the stability of lomustine in aqueous solutions was investigated. All the CDs increased the stability, but two i.e., 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and 2-hydroxyethyl-β-cyclodextrin (HE-β-CD), resulted in a better stabilization than the other CDs tested. Lomustine degraded about 2 to 2.5 times slower within the HP-β-CD-complex than outside it in the solution. © 1990.