3D drug printing

3D drug printing or 3D printing of pharmaceuticals is a technology that uses three-dimensional printing techniques to create customized pharmaceuticals, such as 3D printed tablets. It allows for precise control over the composition and dosage of drugs, enabling the production of personalized medicine tailored to an individual's specific needs, such as age, weight, and medical condition. This approach can be used to improve the effectiveness of drug therapies and to reduce side effects.[1]

## Contents

* 1 Techniques
* 1.1 Fused deposition modeling (FDM)
* 1.2 Stereolithography (SLA)
* 1.3 Binder jet (BJ)
* 1.4 Melt Extrusion Deposition (MED)
* 1.5 Semisolid Solid Extrusion (SSE)
* 2 Formulations and designs
* 3 3D printing of drug-functionalized materials
* 4 See also
* 5 References

## Techniques

The techniques used for printing medication typically involve various additive manufacturing methods, including:

* Fused deposition modeling (FDM)
* Stereolithography (SLA)
* Binder jet (BJ)
* Melt extrusion deposition (MED)
* Semi-solid extrusion (SSE)

These techniques offer various advantages and can be tailored to specific drug formulations and manufacturing requirements.

### Fused deposition modeling (FDM)

The Fused Deposition Modeling (FDM) technology[2] was made available to the public domain in 2009, and is currently a commonly used approach to 3D drug printing. The process begins with a polymer filament that incorporates the drug. This filament is fed through a high-temperature nozzle by two rollers, controlled by computer software to print. Once one layer is complete, the printing platform initiates the next layer. This sequence continues until the entire printing process is finished.[3]

### Stereolithography (SLA)

SLA technology operates on the principle of photopolymerization, utilizing laser scanning to solidify liquid resin and build 3D-printed objects layer by layer.[4] The printing process can be configured to work either from the top to the bottom or vice versa, depending on the printer's setup. To initiate printing, the liquid photopolymer resin is poured into a reservoir, and a scanning mirror focuses a laser beam onto the resin's surface, creating a focused light spot. This light spot solidifies the resin within its swept area. Once a scanning layer is completed, the printing platform lowers by one layer's height, and a squeegee levels the resin surface for the subsequent layer of printing. This process continues until the object is fully formed. Afterward, the finished product is extracted, and any excess resin and support structures are removed. SLA is particularly useful for thermo-labile drugs.[5]

### Binder jet (BJ)

BJ approach begins by spreading a fine layer of powder onto the platform using a roller.[6] Subsequently, a removable printhead sprays droplets, selectively binding the powder to create the desired structure. The platform is then lowered, and a new layer of powder is spread while the printhead continues to deposit droplets. This layer-by-layer printing method repeats until the entire object is formed. Finally, the finished products are extracted, the excess powder is removed, and any necessary post-processing is performed.[7] The printing inks typically contain only the binder, while the powder bed contains the Active Pharmaceutical Ingredient (API) and other supplementary ingredients. In some cases, the API can be introduced into the powder bed as a solution or in the form of nanoparticle suspension. It's worth noting that BJ-3DP technology is not limited to APIs with high water solubility. For APIs that are poorly soluble in water, their solubility can be enhanced through pre-treatment methods, although there is relatively limited research in this area.[8]

### Melt Extrusion Deposition (MED)

MED 3D printing leverages a combination of hot melt extrusion and fused deposition modeling technologies. The process is initiated by introducing active pharmaceutical ingredients (API) and various excipients into separate feeding devices. These materials are then subjected to heat and intense shearing within the hot melt extrusion system, resulting in a uniform molten state.[9] Subsequently, this molten material is delivered to the hot melt extrusion module. The printing stations coordinate their actions, allowing for the amalgamation of diverse molten materials, which are then deposited layer by layer onto the printing platform. Precise control of pressure and temperature results in the creation of 3D-printed preparations that closely replicate the desired structure.

### Semisolid Solid Extrusion (SSE)

Semisolid Solid Extrusion, is an additive manufacturing technique that builds objects layer by layer. In SSE, an extrusion head follows a predefined path, depositing semisolid material to create each layer, and gradually stacking them to form the final product.[10] SSE is conceptually similar to Fused Deposition Modeling (FDM), with a key distinction: the material used in SSE is semisolid at room temperature. This means that precise temperature control is essential during the printing process to prevent excessive softening of the material due to high temperatures, ensuring it maintains its intended shape.

To facilitate this process, a dedicated syringe contains the semisolid print material. The extrusion of the material can be accomplished using various methods, such as pneumatic pressure, mechanical energy, or an electromagnetic system. This technology allows for the creation of complex structures and customized objects by precisely controlling the deposition of semisolid material layer by layer.[11]

## Formulations and designs

The dosage form typically generated by 3D drug printing are tablets and capsules. Various designs have been invented to enable different drug release profiles. 3D printing protocols have been developed to print tablets with immediate-release and modified release profiles.

The order and geometric orientation of layers in a tablet, the shape of tablets, and the excipients used determine the release profile of the active pharmaceutical ingredients.[12]

## 3D printing of drug-functionalized materials

In addition to 3D drug printing which aims at printing drug formulations, 3D printing can be used to fabricate materials functionalized by drugs, e.g., antibiotics or angiogenic agents.[13] This area which is a part of biomaterials engineering, aims at products such as adhesive patches for wound healing, hydrogel, and non-hydrogel implants, rather than tablets or capsules. As such, this field is distinct from 3D drug printing discussed above.

## See also

* Pharmaceutics
* 3D printing
* Pharmacokinetics

## References

1. ↑ "Revolution in Pharmacy: 3D Printed Medicines". March 14, 2023. https://healthnews.com/family-health/drugs/revolution-in-pharmacy-3d-printed-medicines/.
2. ↑ Cailleaux, Sylvain; Sanchez-Ballester, Noelia M.; Gueche, Yanis A.; Bataille, Bernard; Soulairol, Ian (10 February 2021). "Fused Deposition Modeling (FDM), the new asset for the production of tailored medicines". Journal of Controlled Release 330: 821–841. doi:10.1016/j.jconrel.2020.10.056. ISSN 0168-3659. PMID 33130069.
3. ↑ Goyanes, Alvaro; Scarpa, Mariagiovanna; Kamlow, Michael; Gaisford, Simon; Basit, Abdul W.; Orlu, Mine (15 September 2017). "Patient acceptability of 3D printed medicines". International Journal of Pharmaceutics 530 (1): 71–78. doi:10.1016/j.ijpharm.2017.07.064. ISSN 0378-5173. PMID 28750894. https://www.sciencedirect.com/science/article/abs/pii/S0378517317306725.
4. ↑ Deshmane, Subhash; Kendre, Prakash; Mahajan, Hitendra; Jain, Shirish (2 September 2021). "Stereolithography 3D printing technology in pharmaceuticals: a review" (in en). Drug Development and Industrial Pharmacy 47 (9): 1362–1372. doi:10.1080/03639045.2021.1994990. ISSN 0363-9045. https://doi.org/10.1080/03639045.2021.1994990.
5. ↑ Dizon, John Ryan C.; Espera, Alejandro H.; Chen, Qiyi; Advincula, Rigoberto C. (1 March 2018). "Mechanical characterization of 3D-printed polymers". Additive Manufacturing 20: 44–67. doi:10.1016/j.addma.2017.12.002. ISSN 2214-8604. https://www.sciencedirect.com/science/article/abs/pii/S2214860417302749.
6. ↑ Wu, Benjamin M.; Borland, Scott W.; Giordano, Russell A.; Cima, Linda G.; Sachs, Emanuel M.; Cima, Michael J. (1 June 1996). "Solid free-form fabrication of drug delivery devices". Journal of Controlled Release 40 (1): 77–87. doi:10.1016/0168-3659(95)00173-5. ISSN 0168-3659. https://www.sciencedirect.com/science/article/abs/pii/0168365995001735.
7. ↑ Wang, Yingya; Müllertz, Anette; Rantanen, Jukka (14 July 2022). "Additive Manufacturing of Solid Products for Oral Drug Delivery Using Binder Jetting Three-Dimensional Printing" (in en). AAPS PharmSciTech 23 (6): 196. doi:10.1208/s12249-022-02321-w. ISSN 1530-9932. PMID 35835970. https://link.springer.com/article/10.1208/s12249-022-02321-w.
8. ↑ Chen, Grona; Xu, Yihua; Chi Lip Kwok, Philip; Kang, Lifeng (1 August 2020). "Pharmaceutical Applications of 3D Printing". Additive Manufacturing 34: 101209. doi:10.1016/j.addma.2020.101209. ISSN 2214-8604. https://www.sciencedirect.com/science/article/abs/pii/S2214860420305819.
9. ↑ Zheng, Yu; Deng, Feihuang; Wang, Bo; Wu, Yue; Luo, Qing; Zuo, Xianghao; Liu, Xin; Cao, Lihua et al. (1 June 2021). "Melt extrusion deposition (MED) 3D printing technology – A paradigm shift in design and development of modified release drug products". International Journal of Pharmaceutics 602: 120639. doi:10.1016/j.ijpharm.2021.120639. ISSN 0378-5173. PMID 33901601. https://www.sciencedirect.com/science/article/abs/pii/S0378517321004440.
10. ↑ van Kampen, Eveline E. M.; Ayyoubi, Sejad; Willemsteijn, Luc; van Bommel, Kjeld J. C.; Ruijgrok, Elisabeth J. (January 2023). "The Quest for Child-Friendly Carrier Materials Used in the 3D Semi-Solid Extrusion Printing of Medicines" (in en). Pharmaceutics 15 (1): 28. doi:10.3390/pharmaceutics15010028. ISSN 1999-4923. PMID 36678657.
11. ↑ Khaled, Shaban A.; Burley, Jonathan C.; Alexander, Morgan R.; Yang, Jing; Roberts, Clive J. (30 October 2015). "3D printing of tablets containing multiple drugs with defined release profiles". International Journal of Pharmaceutics 494 (2): 643–650. doi:10.1016/j.ijpharm.2015.07.067. ISSN 0378-5173. PMID 26235921. https://www.sciencedirect.com/science/article/abs/pii/S0378517315300855.
12. ↑ "Shape matters: how 3D printing can optimize drug release and effectiveness". IO. 1 August 2023. https://innovationorigins.com/en/shape-matters-how-3d-printing-can-optimize-drug-release-and-effectiveness/.
13. ↑ Zhang, Yue; Wang, Chao (June 2022). "Recent advances in 3D printing hydrogel for topical drug delivery". MedComm – Biomaterials and Applications 1 (1). doi:10.1002/mba2.11.

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