Development of galangal essential oil-based microemulsion gel for transdermal delivery of flurbiprofen: simultaneous permeability evaluation of flurbiprofen and 1,8-cineole

Abstract

Flurbiprofen (FP) is one of the most potent nonsteroidal anti-inflammatory drugs with very low bioavailability of approximately 12% following transdermal administration, compared to that after oral administration. This study aimed to deliver FP as a microemulsion (ME) gel by transdermal administration. Galangal essential oil (GEO) was extracted from Rhizoma Alpiniae Officinarum and identified by GC-MS. The most abundant constituent was determined to be 1,8-cineole (52.06%). Compared to azone, GEO was proved to exert significantly higher (p < .01) penetration enhancement effect and significantly (p < .001) lower skin cell toxicity. The formulation (FP-GEO-ME gel) was prepared using GEO as an oil phase and a penetration enhancer. Compared to that of FP solution, the enhancement ratio (ER) of FP-GEO-ME gel was 4.06. In addition, more than 25% 1,8-cineole permeated through the rat skin. In vivo pharmacokinetic studies revealed that the AUC_0–t of FP after transdermal administration of FP-GEO-ME gel was higher by approximately 4.56-fold than that of marketed FP cataplasms. The relative bioavailability of FP and 1,8-cineole after transdermal administration compared to oral administration of FP-GEO-ME were determined to be 96.58% and 85.49%, respectively. FP-GEO-ME gel significantly inhibited carrageenan-induced hind-paw edema and decreased PGE2 levels in rat serum. GEO-ME gel also exhibited significant anti-inflammatory effects at 2 h after the therapy (p < .05). The synergistic effects of FP and GEO were expected for the application of FP-GEO-ME gel. In conclusion, GEO-ME gel may be a promising formulation for transdermal administration of anti-inflammatory hydrophobic drugs, such as FP.

Keywords:

• flurbiprofen
• microemulsion gel
• pharmacokinetics
• anti-inflammatory effect
• transdermal
• 1,8-cineole
• galangal essential oil

Authors’ contributions

Conceptualization, J.C. and J.D.; Methodology, J.D., X.Z., F.W. and B.Y.; Software, H.F.; Validation, J.C. and J.D.; Formal analysis, Y.D.; Investigation, X.Z. and F.W.; Resources, W.G.; Data curation, J.C. and J.D.; Writing—original draft preparation, X.Z., J.D. and J. C.; Writing—review and editing, J.D. and J.C.; Supervision, J.C.; Project administration, J.C.; Funding acquisition, J.C.

Disclosure statement

The authors declare that there is no conflict of interest regarding the publication of this paper.

Additional information

Funding

This research was funded by the Special Project of Jiangsu Provincial Administration of Traditional Chinese Medicine (ZX2016D1), the Key Project of Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (ZDXMHT-1-15), the Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica (No. JKLPSE201808), the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX18_1591), and the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).