Comparison of the Solubility and Dissolution Rate of Gliclazide-β-cyclodextrin Inclusion Complexes Prepared by Liquid/liquid Extraction and Neutralization
YUNG-KUANG LO, CHU-PING HSU, TONG-RONG TSAI AND THAU-MING CHAM*
Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University
100 Shih-Chuan 1st Road, San Min District, Kaohsiung City 807, Taiwan, R.O.C.
(Received: September 30, 2005; Accepted: April 14, 2006)
ABSTRACT
The solid complexes of gliclazide and β-cyclodextrin were prepared by 2 methods, liquid/liquid extraction and neutralization. The phase-solubility diagram was used to calculate the stability constant of gliclazide and β-cyclodextrin. According to the molar stoichiometry, the complex of gliclazide with β-cyclodextrin was prepared following the 1:1 ratio. The interaction between gliclazide and β-cyclodextrin was analyzed by Fourier-transform infrared spectroscopy and differential scanning calorimetry. The dissolution rate of gliclazide from the complex made by liquid/liquid extraction was faster than those from neutralization method, physical mixtures and pure drug. The mean particle size of two complexes was smaller with a narrower size distribution than those of physical mixtures and β-cyclodextrin. The results indicate that liquid/liquid extraction method, as well as neutralization method, provides some signs of improvement in the solubility and dissolution rate of gliclazide.
Key words: Gliclazide, Cyclodextrin, Liquid/liquid extraction, Neutralization, Solubility