Enhancing Patient-Centric Drug Development: Coupling Hot Melt Extrusion with Fused Deposition Modeling and Pressure-Assisted Microsyringe Additive Manufacturing Platforms with Quality by Design
Abstract
:1. Introduction
2. Pressure-Assisted Microsyringe (PAM)
2.1. Critical Material Properties
2.1.1. Thermal Properties
2.1.2. Rheological Properties
2.1.3. Miscibility
2.1.4. Density of Material
2.2. Critical Instrument Parameters
2.2.1. Type of Piston
2.2.2. Nozzle Size
2.2.3. Cooling Fan
2.2.4. Build Platform
2.3. Critical Process Parameters
2.3.1. Barrel and Nozzle Temperature
2.3.2. Printing Speed
2.3.3. Piston Pressure
2.3.4. Build Platform Temperature
3. FDM 3D Printing
3.1. Critical Material Properties
3.1.1. Mechanical Properties
3.1.2. Surface Morphology
3.1.3. Filament Dimension
3.1.4. Rheological and Thermal Properties
3.2. Critical Instrument Parameters
3.2.1. Gear Rollers
3.2.2. Nozzle Size
3.2.3. Cooling Fan and Build Platform
3.3. Critical Process Parameters
3.3.1. Printing Temperature
3.3.2. Printing Speed
3.3.3. Build Platform Temperature
4. Coupling with HME
5. Quality by Design (QbD) Elements
5.1. Quality Targeted Product Profile (QTPP)
5.2. CQAs
5.3. CMAs
5.4. CPPs
5.5. Risk Assessment
5.6. Control Strategy and Continuous Improvement
- CQAs: CQAs need to be within the established limits to ensure the quality of the product.
- CMAs: The drug substance and the excipient should comply with the specification and satisfy the pre-determined requirements to eliminate any associated risk.
- CPPs: The process needs to be operated within the qualified and validated ranges to prevent any unwanted effects on the CQAs of drug products.
- In-process controls: Throughout the manufacturing process, the critical process parameters must be monitored continuously to ensure they stay within the established range and the intermediate product meets the pre-established specification, directly influencing the CQAs of the final product.
- Specifications: An acceptance criterion needs to be established within the specification to ensure product quality.
- PAT: The implementation of PAT tools will help monitor CMAs and CPPs, which are directly associated with the CQAs of drug products.
- Real-time release testing (RTRT): RTRT involves the in-line testing of the intermediate and finished drug product. Implementing RTRT will increase productivity and reduce costs. For example, the uniformity of the drug within the formulation blend can be monitored by mounting a near-infrared (NIR) probe. This process will ensure the development of a quality and safe medication. Any discrepancies can be controlled immediately without being realized towards the end of the manufacturing during end-product testing.
6. Future Perspectives and Expert Opinion
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nyavanandi, D.; Mandati, P.; Vidiyala, N.; Parupathi, P.; Kolimi, P.; Mamidi, H.K. Enhancing Patient-Centric Drug Development: Coupling Hot Melt Extrusion with Fused Deposition Modeling and Pressure-Assisted Microsyringe Additive Manufacturing Platforms with Quality by Design. Pharmaceutics 2025, 17, 14. https://doi.org/10.3390/pharmaceutics17010014
Nyavanandi D, Mandati P, Vidiyala N, Parupathi P, Kolimi P, Mamidi HK. Enhancing Patient-Centric Drug Development: Coupling Hot Melt Extrusion with Fused Deposition Modeling and Pressure-Assisted Microsyringe Additive Manufacturing Platforms with Quality by Design. Pharmaceutics. 2025; 17(1):14. https://doi.org/10.3390/pharmaceutics17010014
Chicago/Turabian StyleNyavanandi, Dinesh, Preethi Mandati, Nithin Vidiyala, Prashanth Parupathi, Praveen Kolimi, and Hemanth Kumar Mamidi. 2025. "Enhancing Patient-Centric Drug Development: Coupling Hot Melt Extrusion with Fused Deposition Modeling and Pressure-Assisted Microsyringe Additive Manufacturing Platforms with Quality by Design" Pharmaceutics 17, no. 1: 14. https://doi.org/10.3390/pharmaceutics17010014
APA StyleNyavanandi, D., Mandati, P., Vidiyala, N., Parupathi, P., Kolimi, P., & Mamidi, H. K. (2025). Enhancing Patient-Centric Drug Development: Coupling Hot Melt Extrusion with Fused Deposition Modeling and Pressure-Assisted Microsyringe Additive Manufacturing Platforms with Quality by Design. Pharmaceutics, 17(1), 14. https://doi.org/10.3390/pharmaceutics17010014