Rapid analysis of NSAIDs binding to β-cyclodextrin using the simultaneous measurement of absorption and circular dichroism with a novel multi-cell low-volume device.
One of the relatively recent and most widely used approaches to reduce side effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the complexation of NSAIDs with Cyclodextrins (CyD). So far, CyD interaction with drugs is not well understood. There have been many reports along these lines; however, rarely do these studies exploit the full potential of optical techniques. The purpose of this work is to produce a versatile, compact, low-volume, routine apparatus for the simultaneous measurements of absorbance and circular dichroism (CD) which allows for the concurrent use of three different pathlengths for binding studies of NSAIDs/CyD as a function of pH. A new rotating multi-cell holder which holds four cells was designed and manufactured. The work was achieved using an effective novel method for binding titration employing four separate flow cells connected in series in a flow system involving a titration flask and a pump. The pK(a), binding constants, stoichiometry and structural co-conformations of NSAIDs/β-CyD complexes were elucidated and determined with accuracy. The system proved to be efficient and the analysis time was reduced to less than or equal to one fourth of total analysis time used in one-cell systems, with possible automation for high-throughput analysis.
Pharmaceutical Sciences Research Division, King's College London, London, UK. ali.aboel_dahab@kcl.ac.uk
Ali
A
Aboel Dahab
Dhia
D
El-Hag
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002942:Circular Dichroism / Q000295:instrumentation / Q000379:methods*; D004347:Drug Interactions; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D047392:beta-Cyclodextrins