Enhanced Dermal Delivery of Flurbiprofen Nanosuspension Based Gel: Development and Ex Vivo Permeation, Pharmacokinetic Evaluations

Pharm Res. 2021 Jun;38(6):991-1009. doi: 10.1007/s11095-021-03060-6. Epub 2021 Jun 4.


Purpose: The objective of this study was to optimize the Flurbiprofen (FB) nanosuspension (NS) based gel and to investigate the in vitro release, ex vivo permeation, the plasma concentration-time profile and pharmacokinetic parameters.

Methods: FB-NSs were developed using the wet milling process with the Design of Experiment (DoE) approach. The optimum FB-NS was characterized on the basis of SEM, DSC, XRPD, solubility and permeation studies. The dermal gel was prepared by incorporating FB-NS into HPMC gel. Then the in-vitro release, ex vivo permeation studies were performed, and pharmacokinetic studies were evaluated on rats.

Results: The particle size, polydispersity index and zeta potential values of optimum NS were determined as 237.7 ± 6.8 nm, 0.133 ± 0.030 and - 30.4 ± 0.7 mV, respectively. By means of the surfactant content and nanosized particles of the nanosuspension, the solubility of FB was increased about 7-fold. The percentage permeated amount of FB from FB-NS gel (8.40%) was also found to be higher than the physical mixture (5.25%) and coarse suspension (reference) (2.08%) gels. The pharmacokinetic studies showed that the Cmax of FB-NS gel was 2.5 times higher than the reference gel, while AUC0-24 was 2.96 times higher.

Conclusion: FB-NSs were successfully prepared with a wet milling method and optimized with the DoE approach. The optimized FB nanosuspension gel provided better permeation and pharmacokinetic performance compared to FB coarse suspension gel.

Keywords: ex vivo; flurbiprofen; nanosuspension; pharmacokinetic; wet-milling.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Chemistry, Pharmaceutical / methods*
  • Drug Delivery Systems / methods*
  • Drug Development / methods*
  • Drug Liberation / physiology
  • Flurbiprofen / administration & dosage
  • Flurbiprofen / chemical synthesis
  • Flurbiprofen / pharmacokinetics*
  • Male
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry
  • Nanoparticles / metabolism*
  • Organ Culture Techniques
  • Particle Size
  • Rats
  • Rats, Wistar
  • Skin Absorption / drug effects
  • Skin Absorption / physiology*
  • Suspensions
  • X-Ray Diffraction / methods


  • Anti-Inflammatory Agents, Non-Steroidal
  • Suspensions
  • Flurbiprofen