Journal of Inclusion Phenomena and Macrocyclic Chemistry

August 2016, Volume 85, Issue 3, pp 203–216

Effect of loratadine on the dissolution and bioavailability of gliclazide from its hydroxypropyl-β-cyclodextrin complex

Samar H. Thiab  Imad I. Hamdan Dina El-Sabawi Afaf H. Al-Nadaf



Gliclazide (GZD) is a hypoglycemic agent that has slow dissolution rate and variable bioavailability. Inclusion complex of GZD with hydroxypropyl-β-cyclodextrin (HPβCD) was prepared with the molar ratio 1:2 by solvent evaporation method. The complex was characterized using Fourier transform infra-red spectroscopy and differential scanning calorimetry. Solubility and in vitro dissolution studies were performed at acidic and neutral pH values. Furthermore, the competitive interactions of the antihistamine loratadine (LOR) on the binding of GZD to HPβCD were studied by performing solubility and in vitro dissolution studies of GZD-HPβCD complex in presence and absence of the competing drug at pH values 4.5 and 6.8. GZD-HPβCD complex was found to enhance the dissolution of the drug in all pH values studied. The presence of LOR with GZD-HPβCD complex led to some pH dependent changes in the dissolution of the complex which supported the results obtained from the solubility studies. Using blood glucose level as a pharmacodynamic marker that reflects the bioavailability of GZD, in vivo studies have shown that GZD when given as its HPβCD complex together with LOR exhibits about 25 % lower bioavailability (effect) compared to GZD alone. In an attempt to explain the in vivo and dissolution studies, higher order complexes (aggregates) involving LOR, GZD and HPβCD were proposed. The formation of such larger complexes was supported by stoichiometric and diffusion studies.


Hydroxypropyl-β-cyclodextrin, Gliclazide, Loratadine, Dissolution,Displacement
DOI: 10.1007/s10847-016-0620-5