Optimizing paracetamol-ascorbic acid effervescent tablet characteristics: a quality by design approach

Abstract

Objective: This study aims to optimize paracetamol-ascorbic acid (PCM-AA) effervescent tablet characteristics through a Quality-by-Design (QbD) approach, investigating the effects of binder concentration, granulation time, and effervescent agents' ratio on hardness, disintegration, and dissolution of the tablets.

Methods: The QbD approach was implemented by identifying the quality target product profile, critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters for formulating PCM-AA effervescent tablets. An Ishikawa diagram identified risk factors for CQAs. A risk estimation matrix evaluated the levels of associated risks. A central composite design-based response surface methodology with 20 experimental runs, including six center points, identified key factors (binder concentration, granulation time, and effervescent agents' ratio) influencing tablet characteristics (hardness, disintegration, dissolution). The optimum formulation, determined by numerical analysis, was characterized for weight uniformity, tablet thickness and diameter, friability, and PCM and AA assay.

Results: Optimized PCM (500 mg)-AA(200 mg) effervescent tablets with 2.9% PVP concentration, 15 min granulation time, and 1:1.5 (w/w) sodium bicarbonate-citric acid ratio achieved acceptable characteristics (hardness: 45 N ± 20 N, disintegration: <5 min, and both PCM and AA dissolution: <10 min). Model validation showed no significant difference (p > 0.05), indicating consistent results.

Conclusion: The study successfully optimized the hardness, disintegration, and dissolution rate of PCM-AA effervescent tablets via the QbD approach. Granulation time affects hardness and PCM dissolution, binder concentration influences disintegration time, and the effervescent agents' ratio impacts both disintegration time and AA dissolution. This research enhances the understanding of pharmaceutical formulation processes, risk management, and optimization in effervescent tablet development.

Keywords: Effervescent tablets; ascorbic acid; critical quality attributes; paracetamol; quality-by-design.