Formulation Development and Evaluation of Oro-Dispersible Paediatric Paracetamol Tablets

Abstract

Background: Paracetamol is a drug which is administered, both parenterally and orally though mostly orally, for management of pain and fever. Paracetamol liquid dosage forms for paediatrics (syrups and elixirs) dominate the local market despite containing solvents like alcohol and propylene glycol which are not recommended for children. Also, they require large space for storage, high transportation cost, have short shelve lives and are difficult to take accurate measurements at households. In some cases people have opted to cut conventional paracetamol tablets into pieces and administer to children. Oro-dispersible paracetamol tablets are better dosage forms than the liquid preparations. They can be swallowed without using water. They are stable and have improved dissolution and they are a choice for people who have difficult in swallowing and those who refuse to swallow like paediatrics. Objectives: The objective of this study was to develop and evaluate a formulation of oro-dispersible paediatric paracetamol tablets 120mg. Methods: Binary mixtures of paracetamol and the excipients (lactose, starch 1500, crospovidone, croscarmellose, sacharin sodium, magnesium stearate, talc and avicel PH 102) were prepared and stored into the following conditions;-Oven (500C, closed bottle); Climatic chamber (400C/75% RH open bottle) and room condition (300C/75%RH) with open bottle. Samples were evaluated for changes in appearance and odour, assessed by NIR spectrometer and assayed by High Performance Thin Layer Chromatography (HPTLC) at the intervals of 0, 7, 14, 30, 60 and 90 days. Also, paracetamol powder flow was evaluated. Trial formulations containing 80mg and 120mg per tablet of paracetamol were prepared by use of direct compressible excipients (starch 1500 and avicel PH 102). Also, trial batches of the formulation containing 120mg paracetamol were prepared by wet granulation method. Results: Results indicated that paracetamol is compatible with the excipients. Though there were caking for paracetamol: crospovidone and paracetamol: sacharin blends stored at room, oven (500C) and climatic (400C/75%RH) conditions, assay results, NIR spectra and HPTLC densitograms indicated no chemical degradation as there were no trend for assay results, NIR spectra showed no change in shape and there were no additional peaks in densitograms. Also, results indicated that starch 1500 and avicel PH 102 did not improve the flow of paracetamol powder to enable direct compression while maintaining the content of paracetamol at the minimum of 15% w/w of tablet. It was possible to prepare, by wet granulation, trial batches of oro-dispersible paediatric paracetamol tablets 120mg which had acceptable evaluation parameters. Conclusion and recommendations: A formulation of oro-dispersible paediatric paracetamol tablet 120mg has been developed and characterized. This signifies that it is possible for local pharmaceutical manufacturers to develop medicines tailored for paediatrics. Therefore, policy makers should set policy which will change the perspective of local pharmaceutical industries so that they strive to work on WHO recommendations with regard to paediatric formulations. These medicines will benefit paediatrics in terms of ease of use and safety but also minimize the use of resources like transportation cost, storage space and wastage due to stability issues