FORMULATION AND IN VITRO EVALUATION OF DAPAGLIFLOZIN AND SAXAGLIPTIN BILAYERED TABLETS

Abstract

Dapagliflozin (DG) is a sodium glucose cotransporter-2 (SGLT-2) inhibitor and Saxagliptin (SG) is a dipeptidyl peptidase-4 (DPP-4) inhibitor. The aim of the present work is to formulate a bilayered tablet (BT) of DG as immediate release (IR) layer and SG as sustained release (SR) layer by direct compression method for the effective treatment of type 2 diabetes mellitus. Type and concentration of superdisintegrant among [sodium starch glycolate (SSG)/Lycoat RS720/ Ludiflash] was optimized to enhance the dissolution rate (DR) of DG from the IR layer of BT. Type and concentration of SR polymer among (Carbapol 940/ Karaya gum/ HPMC K15M) was optimized to extend the release of SG up to 12 h with zero order release profile from the SR layer of BT. It was concluded that the optimization of the ratio of SG: SR polymer (HPMC K15M), had significant effect on extending the release profiles of SG. The ratio of SG: HPMC K15M at 1:18 respectively forms a better matrix for the extending the release of SG up to 12 h from the SR layer of BT. The optimized formulation; BT9 [IR9 (6% w/w Ludiflash as superdisintegrant and SR9 (with 60% HPMC K15M as SR polymer)] releases 100% of DG from the IR layer with in 45 min and extends the release of SG up to 12 h with a better zero order release profile (r²=0.994). It passes the accelerated stability studies as per ICH guidelines. A combination of these two classes [SGLT-2 inhibitors (DG) and DPP-4 inhibitors (SG)] of glucose-lowering agents and formulating them as a BT is more effective in the treatment and maintenance of type 2 diabetes mellitus.