Cutaneous Drug Delivery of Capsaicin after in vitro Administration of the 8% Capsaicin Dermal Patch System

Abstract

Objective: Epicutaneous application of capsaicin causes a long-lasting analgesic effect by binding to the membrane transient receptor potential vanilloid 1 (TRPV1) on mechanoheat-sensitive C and Aδ fibres, changing axonal integrity and inhibiting neurogenic inflammatory processes. To date, no information is available regarding the cutaneous drug delivery of capsaicin following patch application. Methods: Using a Franz diffusion cell, the cutaneous concentration-time profiles 30, 60 and 90 min after application of a patch containing 8% capsaicin (640 µg/cm²) on ex vivo thin (mamma) and thick (plantar) human skin were investigated at 32°C, and additionally at 42°C for thin skin and 10°C for thick skin. An HPLC-MS method was used for the analytic detection of capsaicin. Results: The results show that already after a 30-min application of the 8% capsaicin patch, an equilibrium reservoir can be found in the stratum corneum in both thick and thin skin. Under physiological temperature conditions, a sufficient bioavailability of capsaicin in the cutaneous target compartments can be found. Raising the temperature to 42°C has no relevant impact on the concentration-time profile, while reducing the temperature to 10°C leads to a significantly lower bioavailability. Conclusion: After 30 min of application, a sufficient cutaneous bioavailability of capsaicin is reached in thick as well as thin skin. Whether shorter application times may suffice to achieve therapeutic effectiveness requires further investigation. © 2014 S. Karger AG, Basel

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

“…Hydrogel, solution, ointment and cream, microemulsion, transfersome, noisome, and liposome preparations of capsaicin have been documented in the literature to treat pain-related disorders such as rheumatoid arthritis, osteoarthritis, diabetic neuropathy, and postoperative pain. 4 – 9 Among them, transfersomes, niosomes, and liposomes are especially efficient to enhance the penetration of capsaicin through the skin and the absorption of the drug into the systemic circulation. Due to its short half-life, the transdermal application of capsaicin needs more frequent replacements in order to achieve satisfactory pain relief.…”

Capsaicin Is a Negative Allosteric Modulator of the 5-HT3 Receptor

“…In topically applied preparations, the concentration of capsaicin ranges between 3 and 260 mM (0.1–8%) ( Bley, 2013 ). Assuming that 2% of topically applied capsaicin is absorbed into the skin ( Lee et al, 1997 ; Wohlrab et al, 2015 ), it is likely that the concentration of capsaicin in the dermis ranges between 60 and 5.2 mM for 0.1% and 8% cutaneous applications, respectively. Importantly, membrane concentration of capsaicin is expected to be greatly higher than that in extracellular compartments due to its high lipophilic structure with a LogP (octanol–water partition coefficient) value of 3.8 ( Rollyson et al, 2014 ; Swain and Kumar Mishra, 2015 ).…”

Ex vivo Cutaneous Bioavailability of Topical Mometasone Furoate in an O/W Preparation

“…The tests were performed on excised human skin from reduction mammoplasty after proof of functional integrity as described previously [45] using a glass Franz diffusion cell (Crown Glass Company, Somerville, NJ, USA). Skin specimens of 3 donors each with 3 pieces of skin per setting and for each application period of 30, 100 and 300 min were investigated.…”