Formulation optimization, physicochemical evaluation and in-vitro stability of ^99mTc labeled with solubilized glibenclamide

Glibenclamide (GBD) is poorly soluble second generation and one of the most potent sulfonylurea derivatives used in the treatment of maturity-onset diabetes as an oral hypoglycaemic agent by inducing insulin secretion in pancreatic β cells. In the present work we have used different concentrations/ratio of solvents to solubilize and form a stable complex of drug with ^99mTc-pertechnetate. The GBD used for the labeling with ^99mTc-pertechnetate was obtained from Micro Advanced Research Centre, Bangalore. To optimize the solubility of GBD we have used different ratio/concentration of the solvents such as PEG 400, ethanol and DMSO (1:1:1, 2:2:1 and 3:3:1). Different concentrations of (50 μg, 75 μg and 100 μg) of the SnCl₂ .2H₂O was added as a reducing agent in the preparation. Dissolved the required quantity of drug (5 mg) in the mixture of solvents (PEG 400, ethanol and DMSO) in 10 ml sterile glass vial. Heat the vial in boiling water bath (5 min, 10 min, 15 min and 20 min) for labeling of drug with ^99mTc. Carried out the physicochemical evaluation of the labeled product (RCP was done in saline Rf = 0.1 and methanol Rf = 0.9). Stability of the drug solution (stored at 2-8 ℃) has been evaluated for its labeling with ^99mTc-sodium pertechnetate at different time points (15 days, 30 days and 60 days). The pH of the product was found 5.0 (± 0.2) with RCP > 98 % (± 1.33) at 0 hr, 6 hr. The solubilized drug was found labeled with ^99mTc-sodium pertechnetate efficiently for the period of 2 months without lyophilization. Labeling of GBD solution with ^99mTc was found stable using optimum concentration of cosolvents without lyophilization. We can reduce the cost of the product by avoiding lyophilization