Study of The Encapsulation of Local Anaesthetic Drugs in Β-Cyclodextrin in Solid and Liquid States
DOI:
https://doi.org/10.48048/tis.2025.9978Keywords:
Cyclodextrin, Anaesthetic drug, UV-Vis spectrophotometry, Procaine hydrochloride, Molecular encapsulation, Differential scanning calorimetry, Isothermal titration calorimetryAbstract
Local anesthetics (LAs) are widely used in medical practice, but their efficacy and stability can be improved through molecular complexation with cyclodextrins (CDs). Beta-cyclodextrin (β-CD), in particular, is known for its ability to form inclusion complexes, enhancing drug solubility and bioavailability. This study explores the molecular interactions between β-CD and three Las - tetracaine (TC), tetracaine hydrochloride (TC·HCl), and procaine hydrochloride (PC·HCl) - using complementary analytical techniques. Since these complexed drugs can be delivered either as liquid-like injections or as solid-like paste and to gain a thorough understanding of the complexation behavior, analyses in both liquid-state (aqueous solution) and solid-state were conducted. Techniques such as ultraviolet-visible spectroscopy (UV-Vis) and isothermal titration calorimetry (ITC) in aqueous solution and differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR) in solid state were used. The UV-Vis and ITC methods gave comparable results regarding the complex formation constants for TC, HCl and PC, HCl complexes but seemed to diverge in the case of basic tetracaine. The ITC data indicated that the 1 site model fits well for TC, HCl/β-CD complex and moderately for PC, HCl/β-CD complex but it was not adapted to the basic tetracaine. The binding process of β-CD with hydrochloride type drugs in liquid state is exothermic, enthalpy controlled and entropy driven since the values of the corresponding binding enthalpies ∆H are negative, fairly lower than of T∆S terms at 298.15 K The solid state characterization of the LA/β-CD complexes by DSC and IR methods showed that the complexation of the hydrochloride LAs into β-CD cavity occurred during both physical mixture and kneading preparations. The IR spectra analysis suggested that the inclusion of hydrochloride type drugs into CD cavity is not exclusively hydrophobic effect driven which probably explains the divergent behavior observed from ITC experiments for the basic tetracaine. IR results supported and completed the conclusions drawn from liquid state investigation.
HIGHLIGHTS
- Host-guest interaction between three anaesthetic drugs and β -cyclodextrin in liquid and solid states
- Complexation studied by spectrophotometry and Isothermal calorimetry in liquid state
- Complexation studied by differential scanning calorimetry and Infra-red spectroscopy for physical mixture and samples obtained by kneading preparation in solid state
- Equilibrium constant (K), enthalpy of complex formation (∆H), the Gibbs energy of complex formation (∆G) and the entropy of complex formation (∆S) have been calculated.
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