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 stability of the compounds in the presence of the cyclodextrins were studied. UV, fluorescence, and several NMR techniques were used to probe the potential causes for the differences observed. The phase solubility method was found to provide only qualitative data on the binding of melphalan to the cyclodextrins since rapid degradation and the presence of products of degradation complicated the interpretation of the results. Qualitatively, however, the solubilizing potential was similar for the two cyclodextrins. The chemical stability studies indicate that both of the drugs had similar binding constants for both cyclodextrins; however, the intrinsic reactivities in the complexes were significantly lower with (SBE)7m-beta-CD than for HP-beta-CD. The main cause for this distinct difference appeared to correlate with differences in the site of binding and the polarity of the binding site.
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Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
Rajewski
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Vander Velde
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Stella
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VJ
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D001665:Binding Sites; D002330:Carmustine / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008558:Melphalan / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D047392:beta-Cyclodextrins
D018906:Antineoplastic Agents, Alkylating; D003505:Cyclodextrins; D005079:Excipients; C103513:SBE7-beta-cyclodextrin; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D008558:Melphalan; D002330:Carmustine