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


Oktay A. N. , İLBASMIŞ TAMER S., Uludag O., Celebi N.

PHARMACEUTICAL RESEARCH, vol.38, no.6, pp.991-1009, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 38 Issue: 6
  • Publication Date: 2021
  • Doi Number: 10.1007/s11095-021-03060-6
  • Journal Name: PHARMACEUTICAL RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, INSPEC, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.991-1009
  • Keywords: ex vivo, flurbiprofen, nanosuspension, pharmacokinetic, wet-milling, NANOSTRUCTURED LIPID CARRIERS, POORLY SOLUBLE DRUG, IN-VITRO EVALUATION, CRITICAL QUALITY ATTRIBUTES, TRANSDERMAL DELIVERY, APIGENIN NANOCRYSTALS, ORAL BIOAVAILABILITY, PROCESS PARAMETERS, PARTICLE-SIZE, FORMULATION
  • Gazi University Affiliated: Yes

Abstract

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 C-max of FB-NS gel was 2.5 times higher than the reference gel, while AUC(0-24) 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.