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

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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.

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Abbreviations

BCS :

Biopharmaceutical Classification System

COX :

Cyclooxygenase

CPP :

Critical Process Parameters

CQA :

Critical Quality Attributes

DoE :

Design of Experiment

FB :

Flurbiprofen

HPH :

High-Pressure Homogenization

NS :

Nanosuspension

NSAID :

Nonsteroidal Anti-inflammatory Drugs

PDI :

Polydispersity Index

PL :

Plantacare 2000

PM :

Physical Mixture

PS :

Particle Size

QbD :

Quality by Design

ZP :

Zeta Potential

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Authors and Affiliations

  1. Department of Pharmaceutical Technology, Gazi University-Faculty of Pharmacy, Ankara, Turkey

    Ayse Nur Oktay, Sibel Ilbasmis-Tamer & Nevin Celebi

  2. Department of Pharmaceutical Technology, University of Health Sciences- Gulhane Faculty of Pharmacy, Ankara, Turkey

    Ayse Nur Oktay

  3. Department of Pharmacology, Gazi University-Faculty of Pharmacy, Ankara, Turkey

    Orhan Uludag

  4. Department of Pharmaceutical Technology, Başkent University-Faculty of Pharmacy, Ankara, Turkey

    Nevin Celebi

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  1. Ayse Nur Oktay
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Oktay, A.N., Ilbasmis-Tamer, S., Uludag, O. et al. Enhanced Dermal Delivery of Flurbiprofen Nanosuspension Based Gel: Development and Ex Vivo Permeation, Pharmacokinetic Evaluations. Pharm Res 38, 991–1009 (2021). https://doi.org/10.1007/s11095-021-03060-6

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