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1st World Conference on Physico-Chemical Methods in Drug Discovery and Development
Gliclazide cocrystals: In vitro and In vivo evaluations
Averinnei R.K, Johan N, Shavi G, Armugam K, Nayak U, Pandey S, Udupa N
Department of Pharmaceutics
Manipal College of Pharmaceutical Sciences
Manipal University, Manipal, 576 104, India
Abstarct
As per the BCS classification gliclazide comes under the category of Class II drugs, the
drugs with low solubility and good permeability. So the present study is aimed at the
preparation of cocrystals with the various carriers such as succinic acid, glutaric acid,
nicotinic acid and tartaric acid with different ratios. Here the cocrystals are prepared by the
slow solvent evaporation method and cogrinding method. The fornmulated cocrystals were
evaluated for the vaious in vitro studies like micromeritic properties (carr’s index, hausners
ratio, angle of repose) drug content, saturation solubility and varoius evaluations using the
differential scanning calorimeter, infrared spectroscopy, scanning electron microscopy and
powder X-ray diffraction. Optimized cocrystals were evaluated for the preclinical
pharmacokinetic and pharmacodynamic studies in the plain and diabetes induced male
wistar rats. Finally the optinmized formulations were compressed into tablets using the
direct compression method. From the results it was observed that there is no incompatibility
between the selected carries and the gliclazide. Compared to the pure drug of gliclazide the
micromeritic properties were greatly improved. The saturation solubility of the gliclazide is
increased about 2 folds compared to the plain drug. From the reuslts of the solubility it was
observed that the slow solvent evaporation method was found to optimum compared to the
cogriding method. The in vitro dissolution studies shows that there is faster release of the
gliclazide in form of cocrystals compared to that of the plain drug. The DSC, IR, SEM and
PXRD studies indicated that there is alteration in the crystal form of the structure and hence
it showed improved solubility and dissoluton. The pharmacokinetic studies shows
improved systemic exposure of the gliclazide in the form of cocrystals compared to the
plain drug. The pharmacodynamic studies shows the percentage reduction of blood glucose
levels in the plain animals are 30.56, 34.03, 53.16 and 61.55 for the cocrystals of gliclazide
prepared with the tartaric acid, succinic acid, glutaric acid and nicotinic acid respectively at
the end of one hour and the normal blood glucose levels were reached at the end of four
hours. Similarly the percentage reduction of blood glucose levels in the diabetes induced
animals are 17.81, 18.40, 22.53 and 23.17 respectively for the cocrystals prepared with
tartaric acid, succinic acid, glutaric acid and nicotinic acid. Based on the in vitro and in vivo
evaluations and considering the stability studies it was concluded that nicotinic acid was a
suitable carrier for the formulation of the gliclazide cocrystals.
Reference:
1. P. Vishweshwar, J.A. McMahon, J.A. Bis, M.J. Zaworotko, Pharmaceutical co-crystals.
J Pharm Sci. 95 (2006) 499-516.