Pharmaceutical formulation and investigations of sustained-release paracetamol matrix tablets and their potential antipyretic effect in children

Background. Paracetamol is widely used as an antipyretic in not only in outpatient, but also inpatient pediatric practice. Overdose with modified-release paracetamol dosage forms creates problems with antidote dose adjustment, which is associated with difficulties in determining the administered toxic dose. In this connection, to investigate various matrix carriers in order to accurately dose paracetamol and to control the rate and degree of its release is an urgent problem. Objective. To formulate 4 different types of paracetamol matrix tablets obtained using 4 polymers, to investigate their effect on the sustained release of the active ingredient, and to assess potential advantages and disadvantages. Material and methods. The behavior of the drug was evaluated using a dissolution test, by modeling of the gastric contents. Results. Four different types of paracetamol matrix tablets were investigated. Two (carbopol and sodium alginate) of the four formulations showed a higher release level than the reference conventional paracetamol tablet. Unfortunately, it was impossible to achieve a model close to zero-order kinetics, and the resultant release was lower than originally expected; with a sodium alginate delivery system, the release of the drug reached a maximum of 50%. Conclusion. It was found that the paracetamol formulations based on carbopol 974P NF and sodium alginate would be useful to enhance drug dose efficiency, by achieving sustained release (via passage through stomach without degradation and via start of its proper release in the intestine), minimizing the risk of side effects, which may as a result improve drug tolerability and a patient’s general condition.

paracetamol, modified release, fever, pediatrics