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

Purpose: Hydroxy propylated &#946 cyclodextrin (HP-&#946-CD) has been used to improve the aqueous solubility of a variety of pharmacological compounds. Through the complexation of HP-&#946-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-&#946-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- &#946-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-&#946-CD resulted in increased solubility at all pH values. But inclusion of drug in the cavity of HP-&#946-CD might depend upon charged state of the molecule. Conclusion: The solubility of gliclazide can be increased either by the addition of HP-&#946-CD or by adding pH lowering agents. Keywords: pH, hydroxypropylated-&#946-cyclodextrin (HP-&#946-CD), gliclazide