Account of analytical techniques employed for the determination of thermodynamics of inclusion complexation of drugs with cyclodextrins

摘要

Inclusion complexation of drugs with cyclodextrins is evolved in the recent past as an important phenomenon to increase the solubility, stability, and bioavailability of drugs along with masking of other undesirable properties, thus making the drug candidate more palatable. Cyclodextrins are known to form non-covalent bonded inclusion complexes with variety of drugs in both solution and solid state with different physical, chemical and biological properties than parent drug or cyclodextrins. Determination of the stability constants of the inclusion complexes is very important. A high value of equilibrium constant (>5000 kg/mol) may lead to very slow release of drug from complex while low value (<200 kg/mol) reduces the effect that inclusion complexation have on the bioavailability of the drug. Wide varieties of analytical techniques are employed to study complexation reaction in solution and solid state. Microcalorimetry is the most precise method for directly measuring the thermodynamic properties of the complex formation. The thermodynamic parameters give a macroscopic picture of the inclusion process.