Application of density functional theory in combination with FTIR and DSC to characterise polymer drug interactions for the preparation of sustained release formulations between fluvastatin and carrageenans

Abstract

In the present study, ι- and λ-carrageenans were used as appropriate carriers for sustained release formulations of fluvastatin drug. From viscosity measurements, it was found that both carrageenans can give miscible blends with fluvastatin due to the interactions between the sulfate groups of carrageenans and hydroxyl groups of fluvastatin. This was predicted by computational analysis using density functional theory and proved by FTIR spectroscopy. These interactions, which are in higher intensity using ι-carrageenan, lead to the formation of complexes between polymeric matrices and fluvastatin drug. DSC experiments also confirmed that miscible blends between carrageenans and fluvastatin can be formed since in all concentrations only one glass transition temperature was recorded. Fluvastatin release depends on the drug content and in all formulations of λ-carrageenans containing 10, 25 and 50 wt% drug, almost sustained release profiles were observed. Fluvastatin/carrageenan complexes have lower dissolution profiles compared with physical mixtures. Polymer swelling seems to be the dominant drug release mechanism. Besides to neat ι- and λ-carrageenans, their blends can be also used as effective matrices for sustained release.

Keywords: Carrageenans; Density functional theory; Fluvastatin; Polymer–drug complex; Sustained release.