Improving the drug load and in vitro performance of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) using polymeric precipitation inhibitors

Int J Pharm. 2020 Feb 15;575:118960. doi: 10.1016/j.ijpharm.2019.118960. Epub 2019 Dec 14.


In this study, the influence of the polymeric precipitation inhibitor (PPI) PVP/VA 64 (polyvinylpyrrolidone-co-vinyl acetate) on the physical stability and in vitro performance of supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) containing the model drug simvastatin (SIM) was investigated. A heating-cooling cycle was employed to dissolve (i) the drug in the SNEDDS preconcentrate, generating super-SNEDDS, or (ii) the drug and PPI generating PPI super-SNEDDS, both containing drug loads of 200% and 250% (with regard to the equilibrium solubility of SIM in the blank SNEDDS). PPI super-SNEDDS were prepared at PPI concentrations of 1%, 10% and 20% (w/w), respectively. The formulations were characterized using polarized light microscopy, dynamic light scattering, rheological profiling and dynamic in vitro lipolysis. The physical stability of PPI super-SNEDDS correlated with an increase in viscosity due to the additionally dissolved PVP/VA 64. PPI super-SNEDDS with drug loads of 200% and 250% containing 20% (w/w) PPI showed no drug recrystallization after more than 6 months of storage at room temperature, whereas PPI-free super-SNEDDS (250% drug load) recrystallized within two hours after equilibration to room temperature. All formulations formed nanosized droplets after emulsification in Milli-Q water. The droplet size was not affected by the PPI, but increased slightly with increasing drug load (z-average of 47.3 ± 0.4 nm for SNEDDS with 200% drug load and 55.6 ± 1.3 nm for SNEDDS with 250% drug load). PPI super-SNEDDS with a drug load of 200% containing 20% (w/w) PVP/VA 64 showed an improved performance during dynamic in vitro lipolysis, maintaining a 2.5-fold higher degree of supersaturation after 15 min of digestion compared to PPI-free super-SNEDDS of the same drug load. In conclusion, the study demonstrated the feasibility of stabilizing higher drug loads and improving the in vitro performance of super-SNEDDS by incorporating PVP/VA 64 into the preconcentrate.

Keywords: Lipid based drug delivery systems (LbDDS); Polymeric precipitation inhibitors (PPIs); Self-nanoemulsiying drug delivery system (SNEDDS); Supersaturated-SNEDDS (super-SNEDDS); Supersaturation.

MeSH terms

  • Crystallization
  • Drug Carriers / chemistry*
  • Drug Stability
  • Emulsions / chemistry*
  • Lipolysis
  • Nanoparticles / chemistry*
  • Particle Size
  • Polyethylene Glycols / chemistry
  • Povidone / chemistry
  • Rheology
  • Simvastatin / chemistry*
  • Solubility
  • Technology, Pharmaceutical / methods*
  • Vinyl Compounds / chemistry
  • Viscosity


  • Drug Carriers
  • Emulsions
  • Vinyl Compounds
  • Polyethylene Glycols
  • Simvastatin
  • Povidone
  • vinyl acetate