Sodium Alginate Beads Containing Epalrestat for Effective Management of Diabetic Mellitus

Abstract

Purpose

Epalrestat is the most common Aldose reductase inhibitor (ARI) approved for blood glucose management in several countries and has also shown efficacy in preventing the onset of diabetic neuropathy (DN), and diabetic retinopathy. The present study aims to formulate and evaluate the effectiveness of Alginate beads of epalrestat in Streptozotocin-induced (STZ) diabetic rats in order to effectively manage the diabetes.

Method

Various formulations of Sodium cross-linked alginate beads containing epalrestat (F1 to F9) were prepared based on full factorial design by ionotropic gelation method. The formulations were characterized for particle size, % Drug entrapment efficiency (DEE), Fourier Transform Infra-Red Spectroscopy (FT-IR), Differential scanning calorimetry (DSC), X-ray Diffraction Study (X-RD), Scanning Electron Microscopy (SEM), and In-Vitro Release Studies. Optimized formulation (F6) [containing sodium alginate (2.5%w/v), epalrestat (2.5%w/v), and calcium chloride (2.5%w/v)] was subjected to in-Vivo efficacy testing in diabetic rats.

Result

Epalrestat-loaded beads were prepared (F1 to F9; Size = 3.21 μm; DEE = 97%) successfully using sodium alginate as polymer and calcium chloride solution as the crosslinking agent by modified ionotropic gelation method Optimized formulation showed a % DEE of 97% and highest drug release of 95% at the end of 10 hrs. Drug Release Kinetic of optimized formulation followed first-order kinetic. Further, the hypoglycemic effect was observed over a longer period 50% reduction after 2 hrs and continued till 4 hrs. In addition, normoglycemia was maintained till 12 hrs (20% reduction) in STZ-induced diabetic rats.

Conclusion

The formulation F6 was found to be superior compared to all the other formulations because the percentage drug entrapment efficiency was highest and there was no chemical interaction took place between the drug and polymer (Confirmed by DSC and XRD studies). In-vivo study showed prolonged hypoglycaemia till 12 hrs with a maximum reduction at 2 hrs Compared to plain drug suspension (20% reduction till 5 hrs).

Read also our introduction article on Alginates here:

excipients formulation