The formulation and evaluation of alcohol-free paediatric paracetamol preparations

Abstract

Paracetamol is currently the analgesic / antipyretic which is most commonly used. It is inexpensive, available without prescription and is relatively safe in therapeutic doses. Since toxic effects are so rare, paracetamol is the drug of choice for treating pain and fever in children. The poor water-solubility of paracetamol, as well as its bitter taste, complicates the formulation of oral paediatric preparations. It has been shown that ethanol increases the risk of paracetamol-induced hepatotoxicity and that its use should be avoided. Various co-solvents were considered as alternative to ethanol for use in aiding the solubility of paracetamol. Six different products were formulated and evaluated. Visual assessment of the samples revealed that only the suspensions stored at 40°C ± 2°C / 75% RH ± 5% RH underwent a change in appearance. Altered versions of validated HPLC methods were used to determine the paracetamol and 4-aminophenol content of the six products. The changes to the methods were essential to remove xanthan gum from the test samples, but gave rise to an unavoidable complication during sample preparation. If not removed from the samples, xanthan gum was found to accumulate in the column. The results obtained from the paracetamol assay weren't reproducible and variation between duplicate samples was substantial in many instances. Though no definite conclusion as to the stability regarding paracetamol content can be made without accurate HPLC results, other tests indicate that the products formulated were stable at room temperature. Furthermore, it could not be shown that either halving the conventional paracetamol concentration (2.4 g / 100 ml), or adding 0.5% v/v ethanol to a formulation had any beneficial effects on product stability. Thus, formulating alcohol-free 2.4 g / 100 ml paracetamol solutions and suspensions can be achieved by using alternative co-solvents in amounts not exceeding their recommended concentrations.