Development and Evaluation of Pediatric Orally Disintegrating Paracetamol Tablets

Abstract

The aim of this study was to develop pediatric orally disintegrating tablets (PODTs) of acetaminophen that would be appropriate for pediatric patients. The limitations of commercially available paracetamol formulations precisely: 1) stability and portability (commercial paracetamol suspensions) and 2) non-pediatric friendly excipients and costly manufacturing processes (commercially available paracetamol orally disintegrating tablets) were addressed by developing tablets using generally regarded as safe (GRAS) status excipients and a direct compression process. A total of eight batches with 60-mg and 120-mg paracetamol strengths of PODTs were successfully prepared by a simple cost-effective direct compression process. The tablets contained crospovidone (5 or 10 %) and/or effervescent excipients (10 or 20%) as disintegrants for fast oral disintegration. The formulated tablets were assessed for uniformity of weight, breaking force, thickness, friability, disintegration time, dissolution, wetting time, water absorption ratio, content and content uniformity. Tablet disintegration rates were found to correlate well with tablet water absorption ratios and to a lesser extent with tablet wetting times. There was no correlation between tablet disintegration times and tablet mechanical and physical properties such as the tablet breaking force (hardness) or friability. Batches that contained 5 or 10% crospovidone disintegrated at a faster rate (of less than 30 seconds) than the effervescent excipients containing batches. The PODT-2 batch with 10% crospovidone was selected as the best batch based on its fast mean disintegration time profile of about 12 seconds. It also had a mean breaking force of 45.8 N as well as a mean friability of 1.6 %. The batch was therefore selected for optimization to reduce its friability and improve its palatability. The batch was successfully optimized as the obtained breaking force led to a reduction in friability without affecting the disintegration time. The palatability was also improved with the addition of sweeteners.