Determination of stability constant values of flurbiprofen-cyclodextrin complexes using different techniques

Area of Science:

• Supramolecular Chemistry
• Analytical Chemistry
• Pharmaceutical Sciences

Background:

• Cyclodextrins (Cyds) are widely used to improve drug solubility and bioavailability.
• Flurbiprofen complexation with Cyds is crucial for its pharmaceutical applications.
• Evaluating different methods for determining stability constants (K(st)) is essential for accurate characterization.

Purpose of the Study:

• To compare three novel experimental techniques with a classic method for calculating the stability constant (K(st)) of flurbiprofen-cyclodextrin complexes.
• To assess the advantages and limitations of membrane permeation, affinity capillary electrophoresis (ACE), and molecular modeling.
• To provide guidance on selecting the most suitable method for investigating various host-guest systems.

Main Methods:

• Membrane permeation technique analyzed via non-linear least-squares method.
• Affinity capillary electrophoresis (ACE) with three linear plotting methods.
• Molecular modeling correlating docking energies with experimental K(st) values.
• Comparison with the classic phase-solubility procedure.

Main Results:

• All methods indicated methyl-beta-cyclodextrin (Me betaCyd) as the strongest complexing agent for flurbiprofen.
• General trend observed: K(st)(Me betaCyd) >> K(st)(HEbetaCyd) > K(st)(betaCyd).
• ACE method showed an inverted trend between HEbetaCyd and betaCyd, likely due to molecular weight influence on electrophoretic mobility.

Conclusions:

• Novel techniques offer valuable alternatives for determining cyclodextrin complex stability constants.
• Method selection depends on the specific host-guest system and experimental conditions.
• Methyl-beta-cyclodextrin demonstrates superior complexation efficacy with flurbiprofen compared to other tested cyclodextrins.