A systematic QbD-Based Approach for the development of baclofen ODTs: Integration risk assessment and factorial design for enhanced patient compliance
DOI:
https://doi.org/10.22317/jcms.v12i3.2185Keywords:
Baclofen, Tablets, Orally Disintegrating, Tablets, Drug Compounding, Drug DesignAbstract
Objective: The current study aimed to prepare baclofen as an orally disintegrating tablet (ODT) to facilitate swallowing in patients with dysphagia. The research utilized the Quality by Design (QbD) framework to identify key formulation variables and optimize the mechanical and physiological properties of baclofen ODT tablets.
Methods: The study begins with risk assessment using the Ishikawa scheme to explore the different process,formulation and environmental factors affecting ODTs. Then, a Plackett-Burman screening design (PBSD) was used to identify the critical independent variables affecting the critical quality attributes (CQAs) of Baclofen ODTs represented by disintegration time (D), hardness(H), and friability (F). Then, a 32 full factorial design was used to optimize the concentrations of significant variables identified by the PBSD.
Results: The most influential factors affecting the quality of Baclofen ODT were successfully identified via Ishikawa analysis. These factors were subsequently quantified through the PBSD and resulted in the finding that Croscarmellose Sodium (CCS) and Microcrystalline Cellulose (MCC) concentrations were the primary determinants of tablet performance. A factorial design was constructed, and 9 formulations were produced. The factorial regression equations developed for friability, hardness, and disintegration time were all statistically significant.Both PBSD and factorial analysis showed that increasing the concentration of CCS significantly prolonged disintegration via gelling-induced pore-blocking. Conversely, increased MCC levels compromised mechanical integrity, resulting in reduced hardness and elevated friability. Numerical optimization identified F3 as the optimum formula since it displayed the highest desirability function (0.74). The optimum formula (F3) has a disintegration time of 22 seconds, a hardness of 5.8 Kg/cm2, and its friability values was 0.25%, respectively.
Conclusion: The study successfully replaced the traditional trial and error concept for ODTs development by adopting a systematic QbD approach . The employment of PBSD coupled with factorial optimization ensured a systematic workflow which can efficiently validate the structural and functional performance of the optimized ODTs.
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