Nouveauté
| Titre : | Quality by Design (QBD) Approach for Tablet Compression Process : Development and Optimization |
| Auteurs : | Mohamed Nadjib Kaarar, Directeur de thèse |
| Type de document : | texte imprimé |
| Editeur : | [S.l.] : Universite ferhat Abbas Setif 1, 2026 |
| Format : | 165p / ill. / 31/21 |
| Accompagnement : | CD ROM |
| Langues: | Anglais |
| Mots-clés: | Quality by Design, Design of Experiments, direct compression, chewable tablet, microcrystalline cellulose, compactibility, design space |
| Résumé : |
Optimization of the Compression Process of an Iron–Vitamin C Chewable Tablet Using a Quality
by Design Approach The industrial handling of a multi-component iron–vitamin C premix intended for stick-pack dosage form revealed severe powder cohesion and flowability defects, leading to repeated screwfeeder blockage. Three corrective attempts (lubrication, screw modification, dry granulation) failed to resolve the underlying poor compactibility of the premix, prompting reformulation toward a chewable tablet produced by direct compression with microcrystalline cellulose (MCC) as a plastic-deforming co-excipient. Given the persistent uncertainty regarding the premix's ability to meet the Quality Target Product Profile, a Quality by Design (QbD) framework supported by Design of Experiments (DoE) was applied to identify the critical process parameters (CPPs) and the critical material attribute (MCC concentration, CMA) governing tablet hardness and friability. A risk assessment (FMEA) prioritized main compression force, pre-compression force, and MCC concentration (10–20% w/w) for experimental investigation. A 2³ full factorial screening design identified MCC concentration and main compression force as the dominant factors, while precompression force showed a statistically significant but non-linear effect, with an optimum at 5 kN. A dedicated 2² full factorial optimization design, complemented by compaction simulation analysis (energy partitioning, force-displacement profiling), established a design space at the upper boundary of the investigated domain (main compression force = 30 kN, MCC = 20%), yielding a predicted hardness of 81.42 N and friability of 1.304%, both within the pharmacopoeially justified acceptance criteria for chewable tablets. Mechanistic interpretation linked the premix's poor tabletability to the brittle, non-slip crystal lattice of ascorbic acid, the fragmentation-dominated bonding of spray-dried mannitol, and the viscoelastic springback of the liposomal iron coating all of which were partially compensated by MCC's plastic deformation and hydrogen-bonding capacity. This work demonstrates that a poorly compressible industrial premix can be transformed into an acceptable chewable tablet through QbD-guided reformulation, while identifying the structural ceiling beyond which further excipient innovation becomes necessary |
Exemplaires
| Code-barres | Cote | Support | Localisation | Section | Disponibilité |
|---|---|---|---|---|---|
| MPH/00816/26 | MPH/00816 | Mémoire | Salle des périodiques | Mémoires de Pharmacie | Exclu du prêt |
