In vitro study of low-frequency ultrasound-enhanced transdermal transport of fentanyl and caffeine across human and hairless rat skin

• Published in: International journal of pharmaceutics Vol. 228; no. 1; pp. 69 - 77
• Main Authors: Boucaud, A, Machet, L, Arbeille, B, Machet, M.C, Sournac, M, Mavon, A, Patat, F, Vaillant, L
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 09-10-2001; Elsevier
• Subjects: Administration, Cutaneous; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - pharmacokinetics; Animals; Area Under Curve; Biological and medical sciences; Caffeine; Caffeine - administration & dosage; Caffeine - pharmacokinetics; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacokinetics; Diffusion; Fentanyl; Fentanyl - administration & dosage; Fentanyl - pharmacokinetics; General pharmacology; Hairless rat skin; Human skin; Humans; In Vitro Techniques; Male; Medical sciences; Membranes - drug effects; Membranes - ultrastructure; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Skin - ultrastructure; Skin Absorption - radiation effects; Sonophoresis; Transdermal delivery; Ultrasonics; Sonophoresis; Fentanyl; Transdermal delivery; Human skin; Hairless rat skin; Caffeine; Human; Pharmaceutical technology; Rat; Biological transport; Rodentia; Permeation; Opiates; Low frequency; In vitro; Lipophilic compound; Vertebrata; Mammalia; Absorption; Animal; Skin; Xanthine derivatives; Hydrophilic compound; Ultrasound; Topical administration
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(01)00820-1

The effect of low-frequency sonophoresis on fentanyl and caffeine permeation through human and hairless rat skin was studied in vitro. Experiments were performed using 20 kHz ultrasound applied at either continuous or discontinuous mode and with an average intensity of 2.5 W/cm
2. The results showed that low-frequency ultrasound enhanced the transdermal transport of both fentanyl and caffeine across human and hairless rat skin. This was explained by both increasing flux during sonication and shortening the lag time. Discontinuous mode was found to be more effective in increasing transdermal penetration of fentanyl while transdermal transport of caffeine was enhanced by both continuous and pulsed mode. Histological and electron microscopy studies showed that human and hairless rat skin was unaffected by ultrasound exposure. Further studies will be necessary to determine the relative contribution of ultrasound parameters in low-frequency ultrasound-induced percutaneous enhancement of drug transport.