Fabrication of prostructured spanlastics gel for improving transdermal effect of dapagliflozin: In vitro characterization studies and in vivo antidiabetic activity

Dapagliflozin is a recently approved glucose-lowering agent for the management of type II diabetes mellitus. Low solubility and stability lead to its poor oral bioavailability. Prostructured spanlastic gel is very less hydrated preform of spanlastic vesicles. Therefore, the aim of this study was to explore the potential of prostructured spanlastic gel for enhancing both drug stability and transdermal delivery. The prostructured spanlastic gel formulations were fabricated by coacervation phase separation method, using Span 60 together with Tween 80 or Myrj 52 as an edge activator. Formulations were characterized for drug content, in vitro release and ex vivo skin permeability. Verification of vesicular form was assessed by hydration and the resultant formulations were characterized. Selected formulations were assessed for morphology, interaction of drug with other components, stability and antidiabetic activity. Drug content percentage of spanlastic gels was found to be in range 98.1 +/- 1.9 to 94.2 +/- 2.0 %. Significant (p < 0.05) increase in drug release rate was observed when edge activator concentration was greater than 30 %. Tween 80 containing formulations exhibited higher skin permeation than Myrj 52 containing ones at the same concentration of edge activator. Spanlastic vesicles were formed by hydration and had entrapment efficiency percentages ranging from 65.06 +/- 0.87 % to 40.36 +/- 0.95 %, mean vesicle sizes ranging from 136.1 nm to 56.52 nm and zeta potential values ranging from -29.7 mV to -6.94 mV. The morphologic examination verified formation of nanovesicular form. Thermal analysis and FT-IR confirmed encapsulation of drug inside spanlastic vesicles. Spanlastic gels showed higher stability and skin permeability when compared to vesicular form in hydroalcoholic gel. Spanlastic gels also showed prolonged hypoglycemic effect and blood glucose level reached below 135 +/- 4.7 mg/dL after 24h, when compared to hydroalcoholic gel (273 +/- 3 mg/dL) and oral suspension (271 +/- 5 mg/dL). In conclusion, spanlastic gel could be a promising carrier for enhancing transdermal delivery of dapagliflozin, offering both sustained and enhanced antidiabetic activity.