Pharmacoscintigraphic evaluation and antidiabetic efficacy of gliclazide-loaded 99mTc-labelled mucoadhesive microspheres

Abstract

Abstract Background The current study was carried out to evaluate the possible application of Musa balbisiana starch in formulation of mucoadhesive microsphere for oral delivery of gliclazide (GLZ). The study objective was to improve the oral bioavailability along with prolongation of its duration of action for a better glycaemic control. Ionic gelation technique was employed in formulating the dosage form. Optimization of the batches was carried out by response surface methodology using 32 full factorial designs. The microsphere prepared was characterized for several parameters along with its in vitro release study. The gastrointestinal transit of the optimized batch of prepared microspheres after oral administration was studied in rabbits by using the gamma scintigraphy technique utilizing 99mTc as the labelling agent in the presence of stannous chloride. Also, the optimized batch was studied for its pharmacokinetic parameters. Moreover, the antidiabetic efficacy of the prepared microsphere was evaluated in rats by using the streptozotocin (STZ)-induced diabetic model. Results The factorial design experiment resulted in an optimum formulation coded as F8. The compatible nature of the drug and excipient was revealed from FTIR, DSC and IST studies. The scanning electron micrographs also showed the occurrence of spherical microspheres having a smooth surface. The in vitro release study provided an evidence of an initial burst effect that was followed by a prolong release phase. The pharmacokinetic parameters justified the ability of the prepared dosage form in sustaining the drug release with a 2.7-fold enhancement in drug bioavailability. The images obtained during the gamma scintigraphy study suggested the gastro-retentive nature of the dosage form with the gastro-retentive ability for more than 4 h. Also, the pharmacodynamics study carried out in diabetic rat model confirmed about the better efficacy of the dosage form in lowering the elevated blood glucose level. Conclusion The overall study data provide valuable information about the potential of this banana starch in formulation of a mucoadhesive dosage form that can be used for enhancement of bioavailability of drug-like gliclazide which in turn can provide a beneficial effect in the management of diabetes.

Keywords

• Gliclazide
• Mucoadhesive microspheres
• Gamma scintigraphy
• 99mTc-pertechnetate
• Ionic gelation