A molecular inclusion complex of atenolol with 2-hydroxypropyl-b-cyclodextrin; the production and characterization thereof

Abstract

The molecular inclusion complex of atenolol with 2-hydroxypropyl-b-cy­clodextrin was synthesized using the coprecipitation method. The complex obtained was characterized by FT-IR, 1H‑NMR, 13C-NMR spectroscopy, as well as by DSC and X-ray diffraction analysis. The DSC analysis confirmed the existence of the com­plex with the endothermic atenolol melting peak at about 155 ºC disappearing. The X-ray diffraction patterns of the complex and 2-hydroxypropyl-b-cyclodextrin were very similar, thus confirming the complete inclusion of the atenolol molecule within the cavity of the 2-hydroxypropyl-b-cyclodextrin. The peaks originating from ate­nolol were completely absent in the diffractogram of the complex. 1H-NMR and 13C-NMR spectra showed certain changes in the chemical shifts of protons and C atoms from atenolol and 2-hydroxypropyl-b-cyclodextrin, indicating that a complex had been formed and also which protons participated in the hydrogen bonds which formed the complex. The atenolol solubility in water was improved (254 mg com­plex cm-3, i.e., 37.5 mg atenolol cm-3), and in pH 3 HCl solution (251 mg com­plex cm-3, i.e., 37 mg atenolol cm-3) when compared to pure atenolol, and even when compared to the atenolol complex with b-cyclodextrin. The increased solubility en­sures greater bioavailability of the active component and, due to the low solubility, significantly corrects for the lack of the basic active substance and, simultaneously, increases its overall therapeutic effect, combined with reduced side effects