A tricyclic, piperidine derivative of antihistamines, loratadine, which belongs in
class II of the Biopharmaceutical Classification System, was investigated. It is an
ionizable drug, whose solubility depends on the gastrointestinal pH, and the bioavailability
is therefore very variable. Inclusion complexes were prepared by kneading method,
containing loratadine (LOR) and dimethyl-beta-cyclodextrin (DIMEB) in two different
molar ratios in an attempt to achieve better dissolution and therefore the better
bioavailability of loratadine. The formation and physicochemical properties of the
inclusion complexes were investigated by means of dissolution tests, pH-dependent
solubility studies, electrospray ionization mass spectrometry and diffusion-ordered
(1)H NMR spectroscopy. The in vivo efficiency of the complexes was examined in rat
animal experiments to confirm the better in vitro dissolution. The instrumental examinations
proved the presence of total complexes in 1:1 ratio in both compositions. However,
the in vitro pH-dependent solubility results, the in vivo blood levels and the greater
pharmacological effect prove that excess DIMEB is needed to achieve the pH-independent
and complete solubility of LOR, and therefore better and more consistent bioavailability.
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