Transdermal delivery of paracetamol for paediatric use: effects of vehicle formulations on the percutaneous penetration

Abstract

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.

Formulation and Evaluation of Bisoprolol Hemifumarate Emulgel for Transdermal Drug Delivery

“…Approximately 1.0 mL samples were taken from each cell of the receptor medium at fixed time periods of 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 8.0, 12.0, 16.0, 20.0, and 24.0 h. Each cell was immediately filled with fresh medium (37 °C). The withdrawn samples were filtered, and the drug quantity was assessed by HPLC at 220 nm (25)(26)(27).…”

Effective use of transdermal drug delivery in children

“…For example the daily, neonatal dose range for paracetamol is 10-30 mg.kg -1 [59,66], which cannot be achieved across the skin. Even when the target delivery rate is more reasonable, careful consideration of the formulation (and, in particular, the use of penetration enhancers) is necessary to minimise the potential for skin irritation.…”

Rapid Informative Screening of Nano-Alaptide as Potential Transdermal Permeation Enhancer of Acetylsalicylic Acid and Paracetamol

“…A similar idea about transdermal delivery systems for acetylsalicylic acid has been discussed recently [24−27]. Also application of paracetamol in a TTS can avoid firstpass hepatic exposure and metabolism via portal circulation and accelerate assembly of action [14,28,29].…”