Development of Oral Lipid Based Nano-formulation of Dapagliflozin: Optimization, in vitro Characterization and ex vivo Intestinal Permeation Study

J Oleo Sci. 2020;69(11):1389-1401. doi: 10.5650/jos.ess20162.

Abstract

The oral route is the most prevalent route of drug administration among various routes. Dapagliflozin is an oral hypoglycemic drug used for lowering the blood glucose level. The objective of this work is to developed and optimized dapagliflozin loaded nanostructured lipid carriers (DG-NLCs) for the improvement of oral delivery. DG-NLCs were prepared by a high-pressure homogenization method (hot) and optimized by Box-Behnken design software using lipid, surfactant, and homogenization cycle as an independent variable. DG-NLCs were evaluated for particle size (Y1), entrapment efficiency (Y2), drug release (Y3). The DG-NLCs were further evaluated for morphology, thermal and X-ray diffraction analysis, ex-vivo intestinal permeation, and stability study. Particle size (nm), entrapment efficiency (%) and drug release (%) of all seventeen formulations were found in the range of 113.71-356.22 nm, 60.43-96.54% and 63.44-83.62% respectively. Morphology of optimized formulation exhibited spherical in shape confirmed by transmission electron microscopy. Thermal and X-ray diffraction analysis of NLCs showed the drug was solubilized and lost the crystallinity. DG-NLCs-opt exhibited dual release pattern initial fast and later sustained-release (90.01±2.01% in 24 h) whereas DG-dispersion showed 31.54±1.87% release in 24 h. Korsmeyer-Peppas model was found to be the best fit model (R2=0.999). The DG-NLCs-opt exhibited significant-high (p < 0.05, 1.293 µg/cm2/h) flux than DG-dispersion (0.2683 µg/cm2/h). Apparent permeation coefficient of DG-NLCs-opt was found to be significantly higher (p < 0.05, 4.14×10-5 cm/min) than DG-dispersion (8.61×10-6 cm/min). The formulation showed no significant changes (p < 0.05) on six months of storage study at 25±2°C/60±5%RH. The finding concluded that quality by design (QbD) based lipid nanocarrier for oral delivery could be a promising approach of dapagliflozin for the management of diabetes.

Keywords: ex vivo intestinal permeation study; Box-Behnken design; diabetes; nanostructured lipid carrier; stability study.

MeSH terms

  • Administration, Oral
  • Benzhydryl Compounds* / chemistry
  • Benzhydryl Compounds* / metabolism
  • Dosage Forms
  • Drug Carriers* / chemistry
  • Drug Compounding*
  • Drug Delivery Systems / methods*
  • Drug Design
  • Drug Liberation*
  • Drug Stability
  • Glucosides* / chemistry
  • Glucosides* / metabolism
  • Hypoglycemic Agents* / chemistry
  • Hypoglycemic Agents* / metabolism
  • Intestinal Absorption*
  • Lipids*
  • Models, Biological
  • Nanoparticles*
  • Nanostructures*
  • Particle Size

Substances

  • Benzhydryl Compounds
  • Dosage Forms
  • Drug Carriers
  • Glucosides
  • Hypoglycemic Agents
  • Lipids
  • dapagliflozin