3D drug printing

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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

Techniques

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

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

Related Research Articles

<span class="mw-page-title-main">Selective laser sintering</span> 3D printing technique

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<span class="mw-page-title-main">3D printing</span> Additive process used to make a three-dimensional object

3D printing or additive manufacturing is the construction of a three-dimensional object from a CAD model or a digital 3D model. It can be done in a variety of processes in which material is deposited, joined or solidified under computer control, with the material being added together, typically layer by layer.

<span class="mw-page-title-main">Organ printing</span> Method of creating artificial organs

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Electron-beam additive manufacturing, or electron-beam melting (EBM) is a type of additive manufacturing, or 3D printing, for metal parts. The raw material is placed under a vacuum and fused together from heating by an electron beam. This technique is distinct from selective laser sintering as the raw material fuses having completely melted.

<span class="mw-page-title-main">Stratasys</span>

Stratasys, Ltd. is an American-Israeli manufacturer of 3D printers, software, and materials for polymer additive manufacturing as well as 3D-printed parts on-demand. The company is incorporated in Israel. Engineers use Stratasys systems to model complex geometries in a wide range of polymer materials, including: ABS, polyphenylsulfone (PPSF), polycarbonate (PC) and polyetherimide and Nylon 12.

<span class="mw-page-title-main">Pharmaceutical manufacturing</span> Synthesis of pharmaceutical drugs

Pharmaceutical manufacturing is the process of industrial-scale synthesis of pharmaceutical drugs as part of the pharmaceutical industry. The process of drug manufacturing can be broken down into a series of unit operations, such as milling, granulation, coating, tablet pressing, and others.

<span class="mw-page-title-main">Powder bed and inkjet head 3D printing</span> 3D printing technique

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<span class="mw-page-title-main">3D bioprinting</span> Utilization of 3D printing to fabricate biomedical parts

Three dimensional (3D) bioprinting is the utilization of 3D printing–like techniques to combine cells, growth factors, bio-inks, and/or biomaterials to fabricate biomedical parts that imitate natural tissue characteristics, form functional biofilms, and assist in the removal of pollutants. 3D bioprinting has uses in fields such as wastewater treatment, environmental remediation, and corrosion prevention. 3D bioprinting can produce functional biofilms which can assist in a variety of situations. The 3D bioprinted biofilms host functional microorganisms which can facilitate pollutant removal. Generally, 3D bioprinting can utilize a layer-by-layer method to deposit materials known as bio-inks to create tissue-like structures that are later used in various medical and tissue engineering fields. 3D bioprinting covers a broad range of bioprinting techniques and biomaterials. Currently, bioprinting can be used to print tissue and organ models to help research drugs and potential treatments. Nonetheless, translation of bioprinted living cellular constructs into clinical application is met with several issues due to the complexity and cell number necessary to create functional organs. However, innovations span from bioprinting of extracellular matrix to mixing cells with hydrogels deposited layer by layer to produce the desired tissue. In addition, 3D bioprinting has begun to incorporate the printing of scaffolds which can be used to regenerate joints and ligaments.

Robocasting is an additive manufacturing technique analogous to Direct Ink Writing and other extrusion-based 3D-printing techniques in which a filament of a paste-like material is extruded from a small nozzle while the nozzle is moved across a platform. The object is thus built by printing the required shape layer by layer. The technique was first developed in the United States in 1996 as a method to allow geometrically complex ceramic green bodies to be produced by additive manufacturing. In robocasting, a 3D CAD model is divided up into layers in a similar manner to other additive manufacturing techniques. The material is then extruded through a small nozzle as the nozzle's position is controlled, drawing out the shape of each layer of the CAD model. The material exits the nozzle in a liquid-like state but retains its shape immediately, exploiting the rheological property of shear thinning. It is distinct from fused deposition modelling as it does not rely on the solidification or drying to retain its shape after extrusion.

<span class="mw-page-title-main">Fused filament fabrication</span> 3D printing process

Fused filament fabrication (FFF), also known as fused deposition modeling, or filament freeform fabrication, is a 3D printing process that uses a continuous filament of a thermoplastic material. Filament is fed from a large spool through a moving, heated printer extruder head, and is deposited on the growing work. The print head is moved under computer control to define the printed shape. Usually the head moves in two dimensions to deposit one horizontal plane, or layer, at a time; the work or the print head is then moved vertically by a small amount to begin a new layer. The speed of the extruder head may also be controlled to stop and start deposition and form an interrupted plane without stringing or dribbling between sections. "Fused filament fabrication" was coined by the members of the RepRap project to give an acronym (FFF) that would be legally unconstrained in its use.

<span class="mw-page-title-main">Applications of 3D printing</span>

In recent years, 3D printing has developed significantly and can now perform crucial roles in many applications, with the most common applications being manufacturing, medicine, architecture, custom art and design, and can vary from fully functional to purely aesthetic applications.

<span class="mw-page-title-main">3D printing processes</span> List of 3D printing processes

A variety of processes, equipment, and materials are used in the production of a three-dimensional object via additive manufacturing. 3D printing is also known as additive manufacturing, because the numerous available 3D printing process tend to be additive in nature, with a few key differences in the technologies and the materials used in this process.

Material extrusion-based additive manufacturing (EAM) represents one of the seven categories of 3d printing processes, defined by the ISO international standard 17296-2. While it is mostly used for plastics, under the name of FDM or FFF, it can also be used for metals and ceramics. In this AM process category, the feedstock materials are mixtures of a polymeric binder and a fine grain solid powder of metal or ceramic materials. Similar type of feedstock is also used in the Metal Injection Molding (MIM) and in the Ceramic Injection Molding (CIM) processes. The extruder pushes the material towards a heated nozzle thanks to

3D printing speed measures the amount of manufactured material over a given time period, where the unit of time is measured in Seconds, and the unit of manufactured material is typically measured in units of either kg, mm or cm3, depending on the type of additive manufacturing technique.

Multi-material 3D printing is the additive manufacturing procedure of using multiple materials at the same time to fabricate an object. Similar to single material additive manufacturing it can be realised through methods such as FFF, SLA and Inkjet 3D printing. By expanding the design space to different materials, it establishes the possibilities of creating 3D printed objects of different color or with different material properties like elasticity or solubility. The first multi-material 3D printer Fab@Home became publicly available in 2006. The concept was quickly adopted by the industry followed by many consumer ready multi-material 3D printers.

<span class="mw-page-title-main">3D food printing</span> 3D printing techniques to make food

3D food printing is the process of manufacturing food products using a variety of additive manufacturing techniques. Most commonly, food grade syringes hold the printing material, which is then deposited through a food grade nozzle layer by layer. The most advanced 3D food printers have pre-loaded recipes on board and also allow the user to remotely design their food on their computers, phones or some IoT device. The food can be customized in shape, color, texture, flavor or nutrition, which makes it very useful in various fields such as space exploration and healthcare.

Abdul Waseh Basit is a professor of pharmaceutics at University College London, and founder of two pharmaceutical biotechnology companies spinning out of UCL. Basit is interested in particular in oral drug delivery and pharmaceutical three-dimensional (3D) printing.

<span class="mw-page-title-main">3D concrete printing</span>

3D concrete printing, or simply concrete printing, refers to digital fabrication processes for cementitious materials based on one of several different 3D printing technologies. 3D printed concrete eliminates the need for formwork, reducing material waste and allowing for greater geometric freedom in complex structures. With recent developments in mix design and 3D printing technology over the last decade, 3D concrete printing has grown exponentially since its emergence in the 1990s. Architectural and structural applications of 3D-printed concrete include the production of building blocks, building modules, street furniture, pedestrian bridges, and low-rise residential structures.

Bioprinting drug delivery is a method of using the three-dimensional printing of biomaterials through an additive manufacturing technique to develop drug delivery vehicles that are biocompatible tissue-specific hydrogels or implantable devices. 3D bioprinting uses printed cells and biological molecules to manufacture tissues, organs, or biological materials in a scaffold-free manner that mimics living human tissue to provide localized and tissue-specific drug delivery, allowing for targeted disease treatments with scalable and complex geometry.

3D printed medicine refers to medicine manufactured using 3D printing technology. It includes 3D printed medications or 3D printed drugs, which are medications that are manufactured using 3D printing technology. 3D printing enables the creation of customized and precise dosage forms tailored to the specific needs of patients. Various technologies have been developed to create 3D-printed medications.

References

  1. ↑ "Revolution in Pharmacy: 3D Printed Medicines". March 14, 2023.
  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.
  4. ↑ Deshmane, Subhash; Kendre, Prakash; Mahajan, Hitendra; Jain, Shirish (2 September 2021). "Stereolithography 3D printing technology in pharmaceuticals: a review". Drug Development and Industrial Pharmacy. 47 (9): 1362–1372. doi:10.1080/03639045.2021.1994990. ISSN   0363-9045. S2CID   239025849.
  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.
  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.
  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". AAPS PharmSciTech. 23 (6): 196. doi:10.1208/s12249-022-02321-w. ISSN   1530-9932. PMID   35835970. S2CID   250560533.
  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. S2CID   219040532.
  9. ↑ Zheng, Yu; Deng, Feihuang; Wang, Bo; Wu, Yue; Luo, Qing; Zuo, Xianghao; Liu, Xin; Cao, Lihua; Li, Min; Lu, Haohui; Cheng, Senping; Li, Xiaoling (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. S2CID   233409105.
  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". 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.
  12. ↑ "Shape matters: how 3D printing can optimize drug release and effectiveness". IO. 1 August 2023.
  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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