Transdermal delivery of paracetamol for paediatric use: effects of vehicle formulations on the percutaneous penetration.
Paracetamol is a safe and effective analgesic and antipyretic agent, and is one of the most widely used medications for infants and children. The formulations currently available have been designed for oral and rectal administration. However, they are not practical in young patients with vomiting and diarrhoea, or in those who refuse to take the full dose. An alternative route of administration would be a significant contribution to the paediatric pharmacopoeia. The aim of this study was to develop a new transdermal system for optional therapeutic administration of paracetamol in infants and children. In-vivo studies were carried out in animals using a transdermal system of high-loaded, soluble paracetamol in a hydrogel patch, which was also tested in-vitro for 8 h. Although the beneficial contribution of glyceryl oleate to the transdermal penetration of paracetamol seemed to be significant in-vitro, it was shown to be insufficient in-vivo. To improve the penetration of the drug, 4% PEG-40 stearate and 10% ethanol were incorporated as absorption enhancers into the dermal patches. A few hours after application of the improved patches to rats, plasma drug concentrations were elevated to levels comparable with those obtained after oral and subcutaneous administration of a high dose of paracetamol. Since plasma drug concentrations did not reach a constant steady state (as a peak or plateau) during the short-term animal experiments, longer pharmacokinetic studies in conscious animals are necessary.
Sintov
Amnon C
AC
The Institutes for Applied Research, Ben Gurion University of the Negev, Beer Sheva 84105, Israel. asintov@bgumail.bgu.ac.il
Krymberk
Igor
I
Gavrilov
Vladimir
V
Gorodischer
Rafael
R
D000082:Acetaminophen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000279:Administration, Cutaneous; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D002368:Castor Oil / Q000737:chemistry / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010372:Pediatrics; D010592:Pharmaceutic Aids / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000187:drug effects*; D013228:Stearates / Q000737:chemistry / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D010592:Pharmaceutic Aids; D013228:Stearates; D000082:Acetaminophen; D000431:Ethanol; D011092:Polyethylene Glycols; D002368:Castor Oil