Improving the Drug Load and in vitro Performance of Supersaturated Self-Nanoemulsifying Drug Delivery Systems (Super-SNEDDS) using Polymeric Precipitation Inhibitors

J Bannow, Y Yorulmaz, K Löbmann, A Müllertz, Thomas Rades

Research output: Contribution to journalArticleScientificpeer-review

23 Citations (Scopus)


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 vitrolipolysis, 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.

Original languageEnglish
Pages (from-to)
JournalInternational Journal of Pharmaceutics
Publication statusPublished - 2020
MoE publication typeA1 Journal article-refereed


  • Polymeric precipitation inhibitors
  • Supersaturation
  • Supersaturated-SNEDDS
  • Lipid based drug delivery systems
  • Self-nanoemulsiying drug delivery system


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