## 1 Introduction  
Pain is a common distress in chronic inflammatory diseases. Rheumatoid arthritis and osteoarthritis are examples of such diseases. The therapy of such diseases depends on the efficacy, safety, and potency of the drug [1]. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for such diseases. Further, it has been observed that cyclooxygenase-2 (COX-2)-selective NSAIDs are better tolerated than and nonselective NSAIDs and have lower side effects [2]. Etoricoxib (ETB) is a highly selective COX-2 inhibitor and has been found to possess fewer adverse effects than other popular NSAIDs, such as indomethacin and diclofenac [3]. Meanwhile, ETB has higher analgesic activity than celecoxib, a selective COX-2 inhibitor. Further, it has about 40% lower gastrointestinal adverse effects compared to other NSAIDs [4]. ETB does not inhibit the production of prostaglandin in the stomach and hence causes the fewer side effects [5]. Importantly, ETB has both anti-inflammatory and analgesic effects, and is very useful in chronic inflammatory diseases. Thus, it is useful against rheumatoid arthritis, osteoarthritis, and acute gouty arthritis [6]. Further, ETB is well tolerated in chronic inflammatory diseases. The therapeutic efficacy of ETB in clinical trials also favors its use in such diseases [7].  
The gastrointestinal ulcers caused by ETB pose a major concern in its oral delivery. Therefore, topical delivery of ETB could be a good choice for the enhancement of its analgesic and anti-inflammatory activities, while decreasing the incidence of gastrointestinal adverse effects [8]. Further, topical delivery can avoid gastrointestinal adverse effects of drugs by directly delivering the drugs to the systemic circulation. Interestingly, the utility of nanoemulsions (NEs) and nanoemulsion gels (NEGs) is well established for the topical delivery of drugs [9; 10]. The small particle size and reduced interfacial tension are some of the advantages of NE in promoting skin permeation. The oil phase helps to solubilize poorly water-soluble drugs. Natural terpene-containing volatile oils have good skin permeability enhancement potential [11]. Eucalyptus oil has analgesic and anti-inflammatory properties and it is a good choice for topical delivery of ETB [12]. Eucalyptus oil mainly contains \(\alpha\)-pinene, \(p\)-cymene, aphellandrene, 1.8-cineole, c-terpinene, and limonene [13]. It is reported that 1,8-cineole enhances skin permeability of both lipophilic and hydrophilic compounds [14].  
Formulation of NE to NEG is needed to render it suitable for application to the skin surface. The thixotropic effects of NEG, due to the presence of the thickening agents, provides product attributes that are appropriate for a topical drug delivery vehicle [15]. Further, modulation of the skin permeation effects of NE is possible by its conversion to NEG. Carbopol polymers are useful for such a purpose. By selecting the appropriate concentration of carbopol 934, it is possible to get a desired topical delivery system [16].  
Commercially available topical gels and creams of ETB are useful in the management of pain and inflammation. Thus, it was anticipated that a NEG formulation would further enhance the therapeutic effect of ETB. Interestingly, a reported study had made such an effort to develop a NEG formulation for ETB [17]. Nevertheless, this reported study used Triacetin as the oil phase and did not explore the possibility of using oils, such as eucalyptus oil. Thus, in the present study, we aimed to develop a NEG formulation of ETB for enhanced analgesic and anti-inflammatory effects by using eucalyptus oil as the oil phase. Moreover, the present study also aimed to evaluate the effects of formulation factors on ETB-loaded nanoemulsion (ETB-NE), which were not explored in the reported study.