Effect of pH and Hydroxylpropyl-b-Cyclodextrin on Solubility and Stability of Gliclazide

Abstract

Purpose: Hydroxy propylated β cyclodextrin (HP-β-CD) has been used to improve the aqueous solubility of a variety of pharmacological compounds. Through the complexation of HP-β-CD, it is possible to enhance the water solubility and hence the drug bioavailability after oral administration. The present study was undertaken to examine the effect of pH and concentration of HP-β-CD on the solubility of gliclazide as it shows pH dependent solubility and stability.
Method: The equilibrium solubility of gliclazide in a series of
solutions of varying pH (from 1.2 to 11) was determined and
compared with the equilibrium solubility of gliclazide in the
presence of 20% HP- β-CD at same pH values.
Result: As the pH increases from 9.2 to 11 its solubility
relatively constant (3.5 μg/ml ± 0.5). Addition of 20% HP--CD
increased the solubility to about 9 times at pH 1.2 and 4; 15
times at pH 6.8; 40 times at pH 7.4; 58 times at pH 9.2 and 67
times at pH 11. It was observed that solubility of protonated
form is more than neutral molecule. HP-β-CD resulted in
increased solubility at all pH values. But inclusion of drug in the
cavity of HP-β-CD might depend upon charged state of the
molecule.
Conclusion: The solubility of gliclazide can be increased either
by the addition of HP-β-CD or by adding pH lowering agents.

Keywords: pH, hydroxypropylated-β-cyclodextrin (HP-β-CD), gliclazide.