3D printed medication

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A 3D printed medication (also called 3D printed medicine, 3D printed pharmaceutical, or 3D printed drug) is a customized medication created using 3D printing techniques, such as 3D printed tablets. [1] 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. [2]

Contents

Applications

Pharmaceutical tablets

The most common application of 3D printing in pharmaceuticals is the production of tablets and capsules. 3D printing offers precise dosing, the ability to design tablets with improved release profiles, and the capability to combine multiple medications into a single tablet. [3] Current developments primarily focus on 3D printing drugs for pediatric, geriatric, psychiatry, and neurology patients, where dosage adjustments are often necessary based on a patient's condition, and patient adherence is a challenge. [4] [5] The first 3D-printed tablet to receive FDA approval was Spritam (levetiracetam), an anti-epileptic medication. [6]

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. [7]

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. [8] 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.

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.

Binder jet

The binder jet approach begins by spreading a fine layer of powder onto the platform using a roller. [9] 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. [10] 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. [11]

Fused deposition modeling

Fused deposition modeling technology [12] 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. [13]

Melt extrusion deposition

Mult extrusion deposition 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. [14] 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

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. [15] 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. [16]

Stereolithography

Stereolithography technology operates on the principle of photopolymerization, utilizing laser scanning to solidify liquid resin and build 3D-printed objects layer by layer. [17] 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. [18]

See also

Related Research Articles

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

Selective laser sintering (SLS) is an additive manufacturing (AM) technique that uses a laser as the power and heat source to sinter powdered material, aiming the laser automatically at points in space defined by a 3D model, binding the material together to create a solid structure. It is similar to selective laser melting; the two are instantiations of the same concept but differ in technical details. SLS is a relatively new technology that so far has mainly been used for rapid prototyping and for low-volume production of component parts. Production roles are expanding as the commercialization of AM technology improves.

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

Stereolithography is a form of 3D printing technology used for creating models, prototypes, patterns, and production parts in a layer by layer fashion using photochemical processes by which light causes chemical monomers and oligomers to cross-link together to form polymers. Those polymers then make up the body of a three-dimensional solid. Research in the area had been conducted during the 1970s, but the term was coined by Chuck Hull in 1984 when he applied for a patent on the process, which was granted in 1986. Stereolithography can be used to create prototypes for products in development, medical models, and computer hardware, as well as in many other applications. While stereolithography is fast and can produce almost any design, it can be expensive.

<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

Organ printing utilizes techniques similar to conventional 3D printing where a computer model is fed into a printer that lays down successive layers of plastics or wax until a 3D object is produced. In the case of organ printing, the material being used by the printer is a biocompatible plastic. The biocompatible plastic forms a scaffold that acts as the skeleton for the organ that is being printed. As the plastic is being laid down, it is also seeded with human cells from the patient's organ that is being printed for. After printing, the organ is transferred to an incubation chamber to give the cells time to grow. After a sufficient amount of time, the organ is implanted into the patient.

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 have completely melted. Selective Electron Beam Melting (SEBM) emerged as a powder bed-based additive manufacturing (AM) technology and was brought to market in 1997 by Arcam AB Corporation headquartered in Sweden.

<span class="mw-page-title-main">Rapid prototyping</span> Group of techniques to quickly construct physical objects

Rapid prototyping is a group of techniques used to quickly fabricate a scale model of a physical part or assembly using three-dimensional computer aided design (CAD) data. Construction of the part or assembly is usually done using 3D printing or "additive layer manufacturing" technology.

<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">Selective laser melting</span> 3D printing technique

Selective laser melting (SLM) is one of many proprietary names for a metal additive manufacturing (AM) technology that uses a bed of powder with a source of heat to create metal parts. Also known as direct metal laser sintering (DMLS), the ASTM standard term is powder bed fusion (PBF). PBF is a rapid prototyping, 3D printing, or additive manufacturing technique designed to use a high power-density laser to melt and fuse metallic powders together.

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

Binder jet 3D printing, known variously as "Powder bed and inkjet" and "drop-on-powder" printing, is a rapid prototyping and additive manufacturing technology for making objects described by digital data such as a CAD file. Binder jetting is one of the seven categories of additive manufacturing processes according to ASTM and ISO.

<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 biomaterials to fabricate functional structures that were traditionally used for tissue engineering applications but in recent times have seen increased interest in other applications such as biosensing, and environmental remediation. Generally, 3D bioprinting utilizes 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. Apart from these, 3D bioprinting has recently been used in environmental remediation applications, including the fabrication of functional biofilms that host functional microorganisms that can facilitate pollutant removal.

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.

4-dimensional printing uses the same techniques of 3D printing through computer-programmed deposition of material in successive layers to create a three-dimensional object. However, in 4D printing, the resulting 3D shape is able to morph into different forms in response to environmental stimulus, with the 4th dimension being the time-dependent shape change after the printing. It is therefore a type of programmable matter, wherein after the fabrication process, the printed product reacts with parameters within the environment and changes its form accordingly.

<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

Computed axial lithography is a method for 3D printing based on computerised tomography scans to create objects from photo-curable resin. The process was developed by a collaboration between the University of California, Berkeley and the Lawrence Livermore National Laboratory. Unlike other methods of 3D printing, computed axial lithography does not build models through depositing layers of material, as fused deposition modelling and stereolithography does, instead it creates objects by projecting a 2D image of the spinning 3D model onto a cylinder of resin spinning at the same rate. It is notable for its ability to build an object much more quickly than other methods using resins and the ability to embed objects within the objects.

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">High-area rapid printing</span>

High-area rapid printing (HARP) is a stereolithography (SLA) method that permits the continuous, high-throughput printing of large objects at rapid speeds. This method was introduced in 2019 by the Mirkin Research Group at Northwestern University in order to address drawbacks associated with traditional SLA manufacturing processes. Since the polymerization reactions involved in SLA are highly exothermic processes, the production of objects at high-throughputs is associated with high temperatures that can result in structural defects. HARP addresses this problem by utilizing a solid-liquid slip boundary that cools the resin by withdrawing heat from the system. This allows for large structures to be fabricated quickly without the temperature-associated defects inherent to other SLA processes.

Bioprinting drug delivery is a method based on the use of 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.

References

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  8. ↑ 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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  14. ↑ 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.
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