In vivo and in vitro evaluation of a solid dispersion system of gliclazide:PEG 6000.
OBJECTIVE
Gliclazide is a potent antidiabetic agent because of its capability to decrease blood glucose level via stimulating endogenous insulin secretion from beta-pancreas cells. Gliclazide is insoluble in water and has low dissolution rate. In this study, polyethylene glycol (PEG) 6000 was used as a matrix to disperse gliclazide in the solid state, and the pharmacokinetic profile of this solid dispersion was studied in rats.


METHODS
The solid dispersion of Gliclazide:PEG 6000 (1:4) was prepared by solvent evaporation method.


METHODS
Samples characterization included differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray diffraction (XRD), and solubility and dissolution test. In vivo study was carried out in healthy rats, randomly. After a single dose of oral administration, blood samples were collected pre-dose (15 min before) and 1, 2, 3, 4, 5, 6, 8, 10, and 12 h post-dose. Plasma concentration of gliclazide was determined by high pressure liquid chromatography method using C-18 column, with mobile phase KH2PO4 (pH 4.6)-acetonitril (40:60 v/v) and UV detection at 229 nm.


RESULTS
Results showed that there were no differences in DSC, IR spectroscopy, XRD, and dissolution test between the solid dispersion and physical mixture. In vivo data showed that the Tmax of gliclazide in solid dispersion and physical mixture was significantly decreased, while the Cmax, AUC(0-12), and AUC(0-infinity) were significantly increased compared to gliclazide alone. These results indicate that the rapid Tmax was due to rapid absorption of gliclazid across the GI tract membrane. Increased Cmax, AUC(0-12), and AUC(0-infinity) indicate a better absorption of gliclazide in solid dispersion and physical mixture than of gliclazide alone.


CONCLUSIONS
Increased in gliclazide dissolution in the presence of PEG 6000 was followed by improved in vivo data.
Asyarie
Sukmadjaja
S
Pharmaceutics Research Group, School of Pharmacy, Institut Teknologi Bandung, Ganesha 10 Bandung 40132, Bandung, Indonesia.
Rachmawati
Heni
H
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D018360:Crystallography, X-Ray; D004337:Drug Carriers; D004339:Drug Compounding; D005907:Gliclazide / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D033362:Powder Diffraction; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D017155:Wettability
D004337:Drug Carriers; D007004:Hypoglycemic Agents; D011092:Polyethylene Glycols; D005907:Gliclazide