Intercalation of olanzapine into CaAl and NiAl Layered Double Hydroxides for dissolution rate improvement: Synthesis, characterization and in vitro toxicity

Abstract

The aim of this work was to develop and characterize different Layered Double Hydroxides (LDHs) loaded with of Olanzapine (OLZ), CaAl:OLZ and NiAl:OLZ, by thermogravimetry (TG), differential scanning calorimetry (DSC), Fourier Transform Infrared spectroscopy (FT-IR) and X-ray diffraction (XRD), dissolution rate improvement, inhibition of AAPH-induced hemolysis and toxicity prospections with Artemia salina assay. No peaks of OLZ were found on diffractograms of both systems (5%) indicating amorphization of OLZ. This behavior was decreased with the increasing of drug. FT-IR spectra showed decreasing, displacements, suppressions and enlargements of bands in specific regions suggesting OLZ intercalation in both HDLs. No OLZ endothermic events was found in DSC curves indicating a decrease in the drug crystallinity, excepting for samples with 30% of OLZ. The dissolution profile evidenced that in 45 min CaAl:OLZ 5% and NiAl:OLZ 5% presented the maximum drug solubilization of 89.08 and 61.66%, respectively. In the inhibition of AAPH-induced hemolysis, both systems, showed significant inhibition (p ≤ 0.05) compared to the negative control, and Artemia salina assay evidenced that both HDLs (5%) did not cause the significant death of the specimens compared to OLZ in 24 h. The exposed results reinforced the proposed use of LDHs as functional excipients.