Encapsulation of methyl and ethyl salicylates by B-cyclodextrin. HPLC, UV-vis and molecular modeling studies

MAURICIO FILIPPA; MATIAS I. SANCHO; ESTELA GASULL

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Elsevier

Año: 2008 vol. 48 p. 969 - 973

0731-7085

The complexation of methyl salicylate (MS) and ethyl salicylate (ES), non-steroidal analgesic,anti-inflammatory and antirrheumatic drugs with B-cyclodextrin (BCD) has been studied from thermodynamic and structural points of view. The complexation with has been investigated usingreversed-phase liquid chromatography. Retention behavior has been analyzed on a reverse-phase column Luna 18(2) 5 um. The mobile-phase was methanol:water in different ratios (55:45 to 70:30) in which BCD (1-9mM) was incorporated as a mobile-phase additive. The decrease in retention times with increasing concentrations of BCD enables the determination of the apparent stability constant of the complexes. Values at 30 °C with 55% methanol were KMS:CD: 15.84M-1 and KES:CD: 12.73M-1 forMS and ES, respectively.The apparent stability constants decrease as the polarity of the solvent decreases. The low solubility of MS and ES in aqueous solution has been improved by complexation with BCD 1-9 mM). The stability constants of the complexes obtained from the phase-solubility diagrams using a UV-vis spectrophotometric method were KMS:CD: 229M-1 and KES:CD: 166M-1. In addition, semi-empirical quantum mechanics calculations using AM1 and PM3 methods in vacuum were performed. The energetically favorable inclusion structures were identified and the most favorable orientation for the inclusion process was found to be the head-down orientation for both complexes. Enthalpy for encapsulation processes was found to be favorable (DHº < 0) while entropy (DSº<0) and Gibbs free energy were unfavorable (DGº > 0) By means of HPLC and UV-vis measurements and quantum mechanics calculations, it was found that MS and ES form a 1:1 inclusion complex with BCD. The theoretical results are in agreement with the experimental parameters associated with the encapsulation process.