Statistical design of experiment-based formulation development and optimization of 3D printed oral controlled release drug delivery with multi target product profile

• Published in: Journal of pharmaceutical investigation Vol. 51; no. 6; pp. 715 - 734
• Main Authors: Than, Yee M., Titapiwatanakun, Varin
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01-11-2021; 한국약제학회
• Subjects: Biomedical and Life Sciences; Biomedicine; Original Article; 약학; Extended-release tablets; Hot-melt extrusion; Hydroxypropyl cellulose; FDM 3D printing; DoE
• ISSN: 2093-5552; 2093-6214
• DOI: 10.1007/s40005-021-00542-y

Purpose
Producing several controlled- release 3D printed tablets from polymer blends with the required target product profile has been a challenge. Thus, experimental design could be applied to rationally explore the impact of the formulation excipients on drug release.
Methods
The optimization of various mixtures under hot-melt extrusion and fused deposition modeling (FDM) printing, using five pharmaceutical polymers [hydroxypropyl cellulose (HPC), Kollidon VA64 (PVP/VA), Soluplus (SLP), Eudragit RS (Eu RS), and RL (Eu RL)], and five disintegrants (sodium starch glycolate, croscarmellose sodium, crospovidone, microcrystalline cellulose, and low substituted hydroxypropyl cellulose), was conducted stepwise. This was followed by rheological, mechanical, and solid-state characterizations to set the critical material attributes, critical process parameters, and critical quality attributes in a D-optimal mixture design.
Results
Eleven extrudable and printable formulations were developed with the support of HPC (3:1 of HPC-PVP/VA, SLP, Eu RS, Eu RL, or disintegrants and 1:1 of HPC-PVP/VA or SLP), 10% indomethacin (IMC), and no plasticizer. The mixture design of nine formulations suggested that drug release was significantly affected by the combined action of different polymers and could predict the optimum formulation (IMC-HPC-PVP/VA-SLP as 10.00:50.45:39.55:0.00) with the required drug release profile at 1, 2, 4, and 12 h.
Conclusion
This work could provide a practical scenario for controlled- release printed systems with quality by design and a more robust filament formulations for FDM printing technology.