Gliclazide is a hypoglycemic agent with poor aqueous solubility that depends on the gastrointestinal pH, and thus it has slow dissolution rate and variable bioavailability. Inclusion complexes of gliclazide with hydroxy-propyl-β-cyclodextrin (HPβCD) were prepared in different molar ratios (1:1 and 1:2) by solvent evaporation method.
The complexes were characterized using Fourier transform infra-red spectroscopy (FTIR), proton neuclear magnetic resonance spectroscopy (1H NMR) and deferential scanning calorimetry (DSC). Solubility and in-vitro dissolution studies were performed at pH values 1.2, 4.5, 6.8 and 7.5. Furthermore, the competitive interactions of gliclazide and two drugs (loratadine and meloxicam) on binding to cyclodextrin cavity were studied by performing solubility and in-vitro dissolution studies at pH values 4.5 and 6.8 for gliclazide-HPβCD complexes in presence of competing drugs. Inclusion complexes of gliclazide with HPβCD were found to enhance its dissolution of the drug in all pH values studied with the complex of 1:2 molar ratio exhibiting the highest improvement.
The presence of loratadine with gliclazide-HPβCD complexes led to significant changes in the dissolution of the complexes, while the presence of meloxicam had no significant effect on gliclazide-HPβCD complexes which confirmed the result obtained from the solubility studies that is meloxicam was weaker than loratadine as competing agent.
For further investigation of the competitive action of loratadine, in vivo study to evaluate the performance of gliclazide-HPβCD complex (1:2 molar ratio) in presence and absence of loratadine was evaluated in rats using blood glucose level as pharmacological marker.
Using gliclazide as HPβCD inclusion complex appeared to decrease the bioavailability of gliclazide compared to non-complexed drugs. The co-administration of loratadine with the gliclazide- HPβCD complex was found to decrease the bioavailability of gliclazide even further, which suggests that loratadine might form higher order of complexes when present with gliclazide- HPβCD complexes. Results were discussed in light of literature.