Influence of copaiba oil on in vitro cutaneous permeability of Celecoxib

Celecoxib (Cxb) delivery on/through skin -topical or transdermal purposes respectively- is an interesting strategy to avoid side effects of oral route. However, its cutaneous penetration is hampered because of the excellent barrier of stratum corneum (SC) and poor aqueous solubility of Cxb [1]. Terpenes are compounds that reduces SC barrier and increases the absorption of drugs on/through skin [2]. Copaiba oil (C.O) is extracted from the tree of Copaifera, and has been used by the natives of Brazil for treatment different disease, including inflammation. Due to the presence of diterpenes and sesquiterpenes in C.O, this oil resin has been explored as penetration enhancer (P.E) [3 – 4]. The aim of this work was evaluate the influence of C.O for improve the delivery of Cxb into skin. Cxb was incorporated in vehicle propylene glycol containing 1 – 50% C.O. In vitro flux (J) of release and in vitro skin permeability were evaluated with synthetic hydrophobic membrane and ear porcine skin, respectively, using Franz diffusion cell system. In vitro release studies showed that increasing the C.O concentration up to 25% increase the amount of Cxb release and the flux (J).The preparation containing 25% C.O released ˜ 100% of Cxb at 24 hours. The amount of Cxb permeated through skin was higher (**p < 0.001) at 25% C.O showing an enhancement ratio (E.R) of 5.75 compared to the control. The amount of the drug into SC was higher at range 5 – 50% C.O (*p < 0.01 to 5 – 10% and **p < 0.001 to 25 – 50%) compared to the control. The retention of Cxb in EP+D was higher at 5.0, 25.0 or 50.0% C.O (**p < 0.001) with an E.R of 5.44, 4.65 and 5.02 respectively. We can conclude that C.O can be a promise adjuvant for delivery Cxb into skin at 5.0, 25.0 or 50.0% for topical applications and at 25% for transdermal delivery. Anyway, C.O has change the skin permeability to Cxb and can be suggested as P.E for its delivery on/through skin.

Fig 1: Amount of Cxb permeated or retained in SC and EP+D (µg/cm²) from preparations containing 1 – 50% C.O or without C.O (Control). Data shown are the mean ± SD. The data were statistically analyzed using One-Way ANOVA (Tukey's multiple comparisons test). Amount permeated through skin at 25% C.O (**p < 0.001) show an enhancement ratio of 5.75. The retained amount in SC at 5% C.O (*p < 0.01) and 25 – 50% C.O (**p < 0.001) show an E.R of 2.87, 4.01 and 6.03 respectively. Amount of Cxb retained in EP + D was higher at 5.0, 25.0 and 50.0% C.O (**p < 0.001) with an E.R of 5.44, 4.65 and 5.02 respectively.

Keywords: celecoxib, copaiba oil, cutaneous permeability

References:

[1] Quiñones OG, Mata dos Santos HA, Kibwila DM, Leitão A, Dos Santos Pyrrho A, Pádula MD, Rosas EC, Lara MG, Pierre MB. In vitro and in vivo influence of penetration enhancers in the topical application of celecoxib. Drug Dev Ind Pharm, published online 4 July 2013; doi:10.3109/03639045.2013.809731.

[2] Ghafourian T, Zandasrar P, Hamishekar H, Nokhodchi A. The effect of penetration enhancers on drug delivery through skin: a QSAR study. Journal of Controlled Release, 99, 113 – 125 (2004).

[3] Almeida MR, Darin JD, Hernandes LC, De Souza Ramos MF, Antunes LM, De Freitas O. Genotoxicity assessment of Copaiba oil and its fractions in Swiss mice. Genetics and Molecular Biology, 35, 3, 664 – 672 (2012).

[4] Oliveira RVM, Ohara MT, Carvalho Vila MMD, Gonçalves MM. In vitro evaluation of copaiba oil as a kojic acid skin enhancer. Brazilian Journal of Pharmaceutical Sciences vol. 46, n. 2, abr./jun., 2010