Ayse Nur Oktay1,2, Sibel Ilbasmis-Tamer1, Orhan Uludag3, Nevin Celebi4,5. 1. Department of Pharmaceutical Technology, Gazi University-Faculty of Pharmacy, Ankara, Turkey. 2. Department of Pharmaceutical Technology, University of Health Sciences- Gulhane Faculty of Pharmacy, Ankara, Turkey. 3. Department of Pharmacology, Gazi University-Faculty of Pharmacy, Ankara, Turkey. 4. Department of Pharmaceutical Technology, Gazi University-Faculty of Pharmacy, Ankara, Turkey. ncelebi51@gmail.com. 5. Department of Pharmaceutical Technology, Başkent University-Faculty of Pharmacy, Ankara, Turkey. ncelebi51@gmail.com.
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 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.
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.
Entities:
Keywords:
ex vivo; flurbiprofen; nanosuspension; pharmacokinetic; wet-milling
Authors: P Langguth; A Hanafy; D Frenzel; P Grenier; A Nhamias; T Ohlig; G Vergnault; H Spahn-Langguth Journal: Drug Dev Ind Pharm Date: 2005-03 Impact factor: 3.225