Novel medium-throughput technique for investigating drug-cyclodextrin complexation by pH-metric titration using the...

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Analytical Chemistry

Background:

• Cyclodextrin (CD) complexation with active pharmaceutical ingredients (APIs) is crucial for drug formulation.
• Accurate determination of CD-API complex stability constants is essential for predicting drug behavior.
• Existing methods for stability constant determination can be time-consuming or require complex measurements.

Purpose of the Study:

• To develop a medium-throughput screening technique for evaluating cyclodextrin-active pharmaceutical ingredient complexes.
• To establish a method for determining 1:1 CD-API complex stability constants (K1:1,CD) using partition coefficients.
• To validate the developed method against orthogonal techniques.

Main Methods:

• Combined dual-phase potentiometric lipophilicity measurement with the partition coefficient method.
• Derived a general equation to calculate K1:1,CD from changes in partition coefficients (logP).
• Utilized experimentally determined logP values of FITC-NH-HPBCD and estimated HPBCD logP to validate the approach.

Main Results:

• Developed a novel method for medium-throughput screening of CD-API complexes.
• Successfully determined K1:1,CD values based solely on partition coefficient changes.
• Introduced a corrected octanol-water phase ratio accounting for complexation effects.
• Obtained K1:1,CD values showed good agreement with orthogonal methods.

Conclusions:

• The developed method offers a reliable and efficient approach for assessing CD-API complex stability.
• This technique simplifies the determination of stability constants, reducing the need for direct API concentration measurements.
• The findings contribute to advancing drug formulation and delivery strategies through cyclodextrin complexation.