Comparative effects of (SBE)(7m)-beta-CD and HP-beta-CD on the stability of two anti-neoplastic agents, melphalan and carmustine

The purpose of this study was to evaluate and compare the potential use of two parenterally safe beta-cyclodextrins derivatives, (SBE)(7m)-beta-CD and HP-beta-CD, as solubilizers and stabilizers for melphalan and carmustine, two very unstable antineoplastic agents. Phase solubility and chemical stab ility of the compounds in the presence of the cyclodextrins were studied. U V, fluorescence, and several NMR techniques were used to probe the potentia l causes for the differences observed. The phase solubility method was foun d to provide only qualitative data on the binding of melphalan to the cyclo dextrins since rapid degradation and the presence of products of degradatio n complicated the interpretation of the results. Qualitatively, however, th e solubilizing potential was similar for the two cyclodextrins. The chemica l stability studies indicate that both of the drugs had similar binding con stants for both cyclodextrins; however, the intrinsic reactivities in the c omplexes were significantly lower with (SBE)(7m)-beta-CD than for HP-beta-C D The main cause for this distinct difference appeared to correlate with di fferences in the site of binding and the polarity of the binding site. (C) 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm S ci 89: 275-287, 2000.