In Vitro Evaluation of Topical Microemulsion of Capsaicin Free of Surfactant

Abstract

Capsaicin (8-methyl N-vanillyl-6 nonenamide), an active compound extracted from Chilli peppers, is widely used for treatment of rheumatoid arthritis, osteoarthritis, diabetic neuropathy and postherpetic neuralgia. 1) However, first pass effect of capsaicin is very high, 2) and the half-life of capsaicin after intravenous administration is only 7.06 min in rats 3) and 12.44 min in rabbits. 4) Adverse events of capsaicin mainly include burning, stinging and erythema at the application site. 5) Topical application of this drug can avoid the first-pass metabolism. Moreover, due to the long period of treatment cycle, 5) topical therapeutical systems (TTS) is very suitable for capsaicin.Microemulsion is a single optically isotropic and thermodynamically stable liquid mixture of oil, water, surfactant and cosurfactant. Due to its advantages, for example, easy making, good stability, enhancing skin permeation and protecting drug against oxidation, 6) microemulsion has become a potential TTS for both hydrophilic and hydrophobic drugs. 7) The structure of microemulsion consists of a disordered, connected surfactant monolayer separating the two solvent domains. It is "balanced" in the sense that this monolayer sheet has no preference in curving toward either of the two solvents. 8) The conditions of microemulsion formation are as follows: (1) very low interfacial tension at the water-oil interface; (2) a highly fluid interfacial surfactant film; (3) the penetration and association of the molecules of the oil phase with the interfacial surfactant film. 9) However, in a microemulsion system, there is commonly a high ratio of surfactants in the formulation, therefore, they may affect the skin barrier function and cause potential risks of irritation and toxicity in long-term application. 10,11) Furthermore, some researches have demonstrated that the increased concentration of surfactant can depress the permeation rate of drugs. [12][13][14][15] This article was intended to investigate the potential of a new microemulsion formulation without surfactant for topical drug delivery of capsaicin. Surfactant-free microemulsions were prepared in other fields, [16][17][18] but were not used in topical pharmaceuticals. The novel microemulsion was based on benzyl alcohol and short-chain alcohol. Benzyl alcohol is a potential transdermal enhancer and has an amphiphilic molecular structure, 19) which is helpful for the formation of microemulsion, 16) and can be used as oil phase in microemulsions. 20,21) Furthermore, benzyl alcohol is a commonly used drug for local anesthesia and alleviating itching, thus, it may be helpful to reduce the side-effects of capsaicin. MATERIALS AND METHODS MaterialsCapsaicin was purchased from Nanjing Tianshu Bioengineering Co., Ltd. (Nanjing, China). Benzyl alcohol (BA), propylene glycol (PG), ethanol (EA) and n-butanol were obtained from Tianjin 1st Chemical Agent Factory. Tween 80 (Polysorbate 80) was purchased from Shanghai Chemical Co., Ltd. Water was double distilled in a quartz inferior-boiling apparatu...

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Characterization of cubosomes as a targeted and sustained transdermal delivery system for capsaicin

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Development, Characterization and Skin Interaction of Capsaicin-Loaded Microemulsion-Based Nonionic Surfactant

“…Capsaicin can release substance P from the afferent nociceptive neurons, and the resulting depletion of substance P desensitizes small afferent sensory neurons. 14) However, orally administered capsaicin undergoes significant first-pass metabolism in rats and mice, 15) and the spiciness of capsaicin limits its clinical applications. Several current studies have reported the topical and transdermal delivery of capsaicin using novel carriers, e.g., niosomes or ME, but these formulations remain limited by their high concentration of capsaicin (0.75% (w/w)) 9) and the use of high levels of ethanol or benzyl alcohol.…”