Driving Forces for the Inclusion of the Drug Tolmetin by β-Cyclodextrin in Aqueous Medium. Conductometric and Molecular Modeling Studies

• Published in: Langmuir Vol. 15; no. 13; pp. 4472 - 4479
• Main Authors: Junquera, E, Mendicuti, F, Aicart, E
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 22-06-1999
• Subjects: Analytical, structural and metabolic biochemistry; Applied sciences; Biological and medical sciences; Complexation; Drug products; Electrostatics; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Hydrophobicity; Ionic conduction; Mathematical models; Molecular dynamics; Natural polymers; Other biological molecules; Physicochemistry of polymers; Starch and polysaccharides; Stoichiometry; Structure (composition); Terpenes, steroids. Hormones; Thermodynamic properties; Stoichiometry; Tolmetin; Control release polymer; Association constant; Drug carrier; Experimental study; Modeling; Non steroidal antiinflammatory agent; Intermolecular interaction; Cyclodextrin; Analgesic; Concentration effect; Molecular model; Oside polymer; Microencapsulation; Aqueous solution; Inclusion compound
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/la9817011

The encapsulation of tolmetin, a nonsteroidal antiinflammatory and antirrheumatic drug, by β-cyclodextrin (β-CD) has been analyzed from thermodynamic and structural points of view, by means of conductometric and molecular mechanics studies. Conductivity measurements of aqueous solutions of tolmetinate (TOL-) were performed as a function of β-CD concentration, at different temperatures ranging from 15 to 40 °C. The stoichiometry of the complex (1:1), its association constant (∼2000 M-1), and the ionic molar conductivities at infinite dilution of the free ( ) and complexed ( ) drug were obtained from these conductivity data. A slightly negative change in enthalpy and a positive change in entropy, obtained from the dependence of K values with the temperature, reveal that both the enthalpy and the entropy favor the inclusion process. Molecular mechanics (MM) calculations, also employed to study the complexation in vacuo and in the presence of water, show that the drug prefers to penetrate into the β-CD cavity by the wider entrance, with toluol group end first. From both MM calculations and experimental results, the hydrophobic effect and electrostatic interactions, possibly arising from the presence of intermolecular hydrogen bonds, seem to have a relevant role in the formation of the β-CD:TOL- complex in aqueous media.