A Review Of 3D Printing Techniques for Dosage Form Development

The pharmaceutical industry stands at the cusp of a technological revolution, driven by the integration of innovative manufacturing techniques that promise to enhance drug formulation, delivery, and personalization. Among these technologies, three-dimensional (3D) printing—also known as additive manufacturing—has gained significant attention for its potential to transform conventional pharmaceutical development and production. Initially utilized in sectors such as aerospace, automotive, and biomedical engineering, 3D printing has now become an emerging tool in pharmaceutical sciences, offering a versatile platform for fabricating complex dosage forms with high precision and customization. 3D printing is defined as the layer-by-layer deposition of materials to create three-dimensional structures based on digital blueprints. This method provides unique advantages over traditional subtractive or molding-based manufacturing techniques, especially in terms of geometric complexity, spatial control of ingredients, and rapid prototyping (1). In pharmaceutical applications, 3D printing allows for the design of dosage forms that are not only functional but also highly personalized—addressing individual patient needs and therapeutic requirements. A key driver for adopting 3D printing in pharmaceutical manufacturing is the growing demand for personalized medicine. Traditional drug formulations are generally manufactured in fixed doses, which may not be optimal for all patient populations. Interindividual variability in genetics, metabolism, age, weight, and disease states often necessitates dose adjustments that are not readily available in standard commercial products. 3D printing enables the on-demand production of dosage forms with tailored drug quantities, release profiles, and physical characteristics, aligning with the principles of individualized therapy (2). This customization is particularly beneficial for special populations such as pediatrics and geriatrics, where swallowing difficulties and variable dosing needs are common. For instance, flexible dosage forms like mini-tablets, chewable tablets, and orodispersible films can be easily fabricated using 3D printing technologies (3). The FDA-approved Spritam® (levetiracetam), developed using ZipDose® technology by Aprecia Pharmaceuticals, exemplifies this innovation. The product dissolves rapidly in the mouth without water, improving adherence among patients with dysphagia and demonstrating the feasibility of 3D printing for large-scale pharmaceutical manufacturing. Furthermore, 3D printing supports the creation of complex and multifunctional dosage forms that are difficult or impossible to produce with conventional methods. These include polypills containing multiple active pharmaceutical ingredients (APIs) with compartmentalized release profiles, as well as devices engineered for site-specific or timed drug release (4). By enabling intricate internal architectures such as porous matrices, honeycomb structures, and multilayered arrangements, 3D printing can facilitate both immediate and controlled-release formulations in a single unit. The efficiency and flexibility of 3D printing also enhance the early stages of drug development. Traditional pharmaceutical manufacturing often requires extensive formulation trials and retooling, which are time-consuming and resource-intensive. In contrast, 3D printing allows researchers to rapidly prototype and iterate dosage designs with minimal material wastage and reduced lead times (5). This accelerated development process is especially valuable in clinical settings, compassionate use programs, or niche markets where demand for customized treatments is high but commercial incentives may be limited. Another significant advantage of 3D printing is its alignment with on-demand and decentralized manufacturing models. As healthcare systems move toward localized treatment solutions and precision healthcare, 3D printing offers the potential for point-of-care drug manufacturing in hospitals, pharmacies, or even home settings (6). This decentralization could mitigate supply chain disruptions, reduce storage needs, and enable real-time customization based on current patient data. Moreover, 3D printing opens avenues for integrating digital health technologies into pharmaceutical care. Coupled with electronic health records, wearable sensors, and pharmacogenomic information, 3D printers could theoretically adjust dosage forms based on real-time patient monitoring, ushering in an era of "smart medicine" where therapy dynamically responds to physiological feedback (7). Despite its promise, the implementation of 3D printing in mainstream pharmaceutical manufacturing is still in its early stages and faces several challenges. Regulatory uncertainties remain a significant barrier, as quality assurance, validation protocols, and reproducibility standards for 3D-printed drug products are still under development. In addition, the range of excipients and APIs compatible with various printing techniques (e.g., fused deposition modeling, inkjet printing, selective laser sintering) is currently limited, necessitating further research into printable pharmaceutical-grade materials (8). Nonetheless, ongoing advancements in formulation science, material engineering, and regulatory policy are gradually addressing these limitations. As more data emerge regarding the stability, safety, and efficacy of 3D-printed dosage forms, it is anticipated that the adoption of this technology will expand across the pharmaceutical value chain—from research and development to manufacturing and personalized delivery. Thus, this review focuses on the various 3D printing techniques and their advantages and limitations in pharmaceutical dosage form development.

Fixed Dose Combination:

Fixed Dose Combination (FDC) products are pharmaceutical formulations that contain two or more active pharmaceutical ingredients (APIs) combined in a single dosage form. The primary rationale behind FDCs is to improve patient adherence by reducing the tablet burden, especially in chronic conditions such as hypertension, diabetes, HIV/AIDS, and tuberculosis (9). For example, commonly prescribed fixed dose combinations (FDC) of antihypertensive drugs that are available in the market are shown in Table 1. Calcium channel blockers, diuretics, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) are the three main classes of drugs that are considered as first line of therapy in hypertension. FDC medications have several benefits, including treatment simplification and a decrease in patients' tablet burden, which are essential for the treatment of hypertension. Many studies have demonstrated that using a combination product improves blood pressure reduction and boosts therapeutic adherence. Moreover, no rise in adverse effects have been observed (10). By simplifying complex therapeutic regimens, FDCs enhance treatment efficacy and minimize the risk of missed doses, which is particularly critical for diseases requiring long-term therapy. FDCs also contribute to improved pharmacokinetic and pharmacodynamic profiles by combining synergistic or complementary agents, allowing for optimized therapeutic outcomes. However, developing FDCs presents challenges such as drug-drug interactions, stability issues, and ensuring consistent bioavailability of all components. However, there are some limitations with the FDC, one of them being a decrease in prescription flexibility. The usage of FDC may limit the ability to alter the dosages of specific medications and the patients are exposed to unnecessary therapy. It can be challenging to determine the precise source of any unexpected side effect. Also, it is challenging for physicians to remember every FDC's precise contents when writing prescriptions. Finally, FDC generally cost more than free generic antihypertensive drugs (11). Despite these hurdle, regulatory bodies like FDA and WHO recognize the value of FDCs and have established specific guidelines to ensure their safety and efficacy.

In the field of precision medicine, medical practitioners refer to the patient’s genetics, lifestyle, and environment to determine the best possible approach to treat the disease (12). The susceptibility and reaction to a certain therapy will vary from patient to patient, thus leading to a customized medical treatment that is unique for every patient. The power of precision medicine resides in its potential to guide medical professionals toward the most efficient therapeutic treatment option for a specific patient and thus, elevate the quality of care (13). Precision medicine makes it possible to give the right doses and release times of relevant medications for each patient, who has various extents of different diseases and also allows the medical practitioner to provide a single medication that combines multiple drugs depending on the patient's characteristics with an appropriate dosage and release profile (14).  Tablets are still considered the most accepted and cheapest oral dosage forms, so instead of taking many tablets at various times throughout the day, the combination of medications in a single tablet can be taken once. One of the concepts for individualized therapy is tablet scoring, which refers to the breakage of a tablet to attain a desired efficacy dose. But the results of splitting of tablets have shown that the breaking of scored tablets often leads to deviations in segment mass and drug content (15). Tablet splitting devices are sometimes assumed to enable more accurate splitting, but the use of these tools does not necessarily lead to exact divided doses (16). Still, the risk is reduced by using these medical devices if compared to a knife or breaking by hand. After summarizing the studies on tablet splitting, it can be concluded that scored tablets might provide a reasonable opportunity for individualized dosing but is still a risky practice in terms of adequate dosing and potential poisoning. Usually only four different doses can be obtained from a conventional tablet, which does not really match the term individual therapy(10, 15-17). For the approach of precision medicine to be effective, the tablets need to be easily fabricated, customizable, and highly affordable which would encourage widespread usage and allow it to be fabricated on the spot after diagnosis. However, the customization of materials is challenging, tedious, and may be costly. 3D printing technology can potentially be a method for overcoming the challenges of small-scale fabrication as it allows tablets to be fabricated easily and quickly at a relatively lower cost (15).

3D Printing:

With the vision of personalized medicines becoming a reality, there is a crucial need to develop technologies that enables the transition away from the conventional large-scale production of fixed strength medicines towards creating personalized dosage forms and dose combinations on demand. This transition can be enabled by 3D printing technology, producing tablets that are individualized to a patient’s therapeutic requirements like dosage, drug combination and drug release profiles as well as personal preferences such as shape, size, texture, and flavor (10, 18). 3D printing is one of the innovative technologies in product manufacturing and design which involves the conversion of digital models into physical objects. It is also known as Additive Manufacturing or Rapid Prototyping or Layered Manufacturing (19). The first ever 3D printer was commercialized by Charles Hull in 1980. Hull came up with the first ever commercially available 3D printer termed as “SLA-250”, that gave rise to an innovative idea of 3D printing (20). However, the first ever patent for the apparatus which was termed “3D printer” was obtained by MIT professors, Emanuel Sachs and Michael Cima in 1993 for the printing of metal, ceramic, and plastic parts (21). Ever since its first appearance, this technology has revolutionized various research industries such as automobile, construction, biomedical, toy, food, chemical, and pharmaceutical industries (22).  The process of 3D printing for tablet production can be described as the ‘3 Ds of 3D printing’ which includes design, develop, and dispense. A digital computer-aided design (CAD) software is used to design the intended parts. The CAD file describes the geometry and the size of the intended parts to be built. The CAD file is then digitally transferred to the selected 3D printer. This process involves the conversion of 3D models into stereolithography (STL) file format, which is further communicated to 3D printer, allowing for precise fabrication. The information about the dimensions of the parts in use and their geometries and coordinates of the triangles would be provided by CAD-file and .STL files respectively which eventually result in making up the surface of the designed 3D model (23, 24). In the next step, tablets are developed by feeding a mix of drug and excipients into the selected 3D printer. The most appropriate printing parameters that are selected for e.g., resolution, temperature, hatch space and printing speed, are typically based on the printer type, drug characteristics and desired outcomes. In the final step, the 3D printer is then ready to print the formulation layer by layer, printing the final tablets (25).

3D Printing in Drug Development:

3D printing is a step towards personalization of required medication for customization to individuals. Fixed dose combinations that are commercially available represent the required dose for safe and therapeutic effect in average patients. Here, the goal is to move away from one size-fits all approach to personalized medication considering different factors such as physiology, concurrent therapy, drug response, genetic makeup, and disease state (26). The vision of personalized medication is to enable the transition from traditional large-scale production of fixed strength medicines to creating flexible and personalized dosage forms and dose combinations on demand. The technology can be used to develop medicines that are specific to a patient’s therapeutic requirements such as dosage, drug combination and drug release patterns and personal preferences such as shape, size, texture, and flavor.  Thus, it is possible for a pharmacist to manufacture tablet using a 3D printer on a small scale to fulfill the needs of the patient having an unusual dosage requirement that is not currently available on the market (27). By customizing medications, either by mixing different drugs into a single tablet or by selecting the appropriate doses, it may lead to an increase in medication adherence, decrease adverse drug responses, and improve therapeutic results (28). This novel approach allows precise and controlled integration of multiple active pharmaceutical ingredients (APIs) into a single tablet, tailored to the specific needs of patients. This personalized approach can enhance medication adherence, simplify dosing regimens, and optimize therapeutic outcomes for patients with complex diseases. Also, 3D printing enables the production of customized drug formulations based on individual patient requirements, such as personalized dosages or modified release profiles. Initially, the pharmaceutical industry was slow to adopt 3D printing technique however the approval of Spritam® (Levetiracetam) tablet by the USFDA in 2015, manufactured using 3D printing technology has catalyzed remarkable surge in the studies pertaining to 3D printed medicines (29). There has been a significant shift in the pharmaceutical manufacturing field, with an increasing number of experts now dedicated to preparing the drug products using 3D printing technologies. This shift has not only sparked the surge in the number of published studies focusing on 3D printing but also facilitates regular sharing of updated knowledge about 3D printing technologies (30).

Types Of 3D Printing:

Binder Jet Printing

The first 3D printing technology used in pharmaceutical application was inkjet printing, also known as binder jet printing. The system comprises of a powder reservoir, binder reservoir, print head and the build platform. With this technology, the powder is discharged from the reservoir on the build platform and a liquid binder solution can be deposited on the powder bed to create the desired geometrical object (31). In this technique, two horizontal X-Y axes are positioned over a vertical piston called the print head, which can be controlled by computer. The powder bed is covered with a small layer of powder to start the process. The print head on top of the powder bed is fed with liquid binder solution which moves back and forth over the powder bed to selectively print droplets that bind the powder particles together to create the desired pattern. Another thin layer of powder is deposited when the powder bed is lowered at a specific distance along the Z-axis, and the procedure is repeated sequentially (32). This method is based on the selective deposition of binder droplets on a thin layer of powder through the print head which can be position and motion-controlled, following the given instructions of the CAD model, and enables to bind the powder particles consisting of excipients and/or drug together (33). API with additional excipients may be present in the powder bed and the liquid formulation inside the print head may only consist of a binder. Alternatively, APIs can also be jetted onto the powder bed as solutions or nanoparticulate suspensions. Spritam, the first 3D-printed drug approved by FDA, was created using this method and approved in 2015 (2). This technique provides high resolution which enables the formation of complex structures and is also capable of producing immediate release as well as sustained release formulations (25, 34). However, binder jet printing is an expensive process and suffers from lack of portable equipment.

Figure 1 Schematic Representation of Binder Jetting Printing

Inkjet printing has been broadly used for creating highly porous 3D objects. In this method special consideration about the physicochemical properties such as viscosity, particle size of powder being used for printing are investigated. Transformations concerning wet granulation method are very likely to occur during the printing process depending on the physicochemical properties. Inkjet printing can be further classified into drop-on-demand inkjet printing and continuous inkjet printing. Based on the type of the printhead drop-on-demand printer is further sub classified into piezoelectric inkjet printer and thermal inkjet printer (35-37). Acosta-Velez et al. used inkjet printing technology with piezoelectric nozzle for formulation of naproxen tablets using polyethylene glycol diacrylate as a polymer (38).

Pressure Assisted Micro Syringe

Pressure assisted micro syringe (PAM) type of 3D printing technology has a broad range of applications in tissue engineering and is generally used to build soft tissue scaffolds. PAM technology is not subjected to very high temperatures unlike other 3D printing methods. Here the semi-solid materials in the form of pastes or gels are extruded with the help of syringe-based tool-head which will eventually form a series of sequential layers to obtain a desired 3D construct. Drying is a crucial post-printing parameter in this type of technology because of the usage of various excipients, solvents and polymers, as inappropriate drying would directly affect the final product to deform or shrink. Additionally, the deposited layer during the printing process must strengthen enough to handle the weight of succeeding layers, otherwise the printed object would collapse (39, 40). Algahtani et al. prepared dapagliflozin containing self-nanoemulsifying tablets using PAM technology of 3D printing (41).

Semi-Solid Extrusion

Semi-solid extrusion (SSE) based 3D printing is an emerging additive manufacturing technique utilized in pharmaceutical dosage form development. Unlike traditional 3D printing methods that rely on thermoplastic materials, SSE uses viscous, paste-like formulations which are extruded through a nozzle to form three-dimensional structures layer by layer. This technique is particularly advantageous for printing heat-sensitive active pharmaceutical ingredients (APIs) and allows for the incorporation of a wide variety of excipients and polymers that enhance drug stability and release profiles (1). Moreover, SSE enables the fabrication of personalized medicines, such as patient-specific doses and multi-drug formulations, supporting the paradigm shift toward precision medicine (42). The versatility, cost-effectiveness, and ease of implementation make SSE a promising technique for on-demand drug manufacturing and localized production in clinical settings. In SSE based 3D printing, a drug-loaded semi-solid material is extruded using a syringe-based tool head. The printer head is moved along the X-Y-Z axis to release the extrudate, which solidifies at room temperature onto a build plate. The technique is suitable for production of chewable and palatable formulations and is capable of producing a range of formulation types, including immediate-release and controlled release dosage forms, polypills and oral films. Limitations include low resolution compared to other 3D printing technologies, limited suitability only for drugs that can be formulated as semi-solids and low throughput.

Fused Deposition Modelling (FDM)

FDM is considered the most commercialized 3D Printing technology as it is a simple, straightforward process and cost effective. This approach is an example of material extrusion process. In this process, a thermoplastic drug loaded filament is prepared using hot melt extrusion. Subsequently, the filament is fed into an extruder equipped with rollers and then connected to a heated nozzle. The print head is then moved along the X-Y axis to discharge the molten extruded filament, which solidifies upon contact with the build plate at room temperature. While printing the tablet, the build plate is incrementally lowered along the Z-axis, equivalent to the thickness of a single layer, enabling the tablet to be printed layer by layer. (18, 25, 43). There are several pharmaceutical grade polymers used in FDM technology such as ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl methyl cellulose acetate succinate, ethylated acrylate copolymer, polyethylene glycol, polyethylene oxide, polylactic acid, polyvinyl alcohol (PVA), and polyvinyl pyrrolidone. Amongst these polymers, PVA is widely used in 3D printing of medicines through FDM technology as it is approved by FDA and is biodegradable. The challenges with this technology include a risk of degradation of the thermally sensitive drugs during processing at high temperatures, relatively low resolution of the printed objects and this process is also dependent on the mechanical properties of the filament (43, 44).

Figure 2 Schematic Representation of Fused Deposition Modelling

SLA, a vat polymerization technique, was the first technology in the history of 3D printing invented by Charles Hull in 1980 and is widely used in the field of tissue engineering (45). In this process, a photopolymerizable liquid resin is filled in the body of the printer with a build plate which moves along the Z axis inside the resin. It is then exposed to a high-energy source of light, usually in the UV spectrum. When the build plate is lowered, the lasers sweep across it, which will induce polymerization and solidification of the material on the build plate which is present at the top of the resin. The build plate will be further lowered, and the lasers will sweep repeatedly building the 3D object layer by layer according to the defined pattern in the CAD file (25, 46, 47). This process offers several advantages, including exceptional surface finish and resolution, reduced print times, and high versatility, as the active pharmaceutical ingredient (API) can be easily mixed with the photopolymer prior to printing, enabling it to be encapsulated within the solidified matrices. Moreover, localized heating during the printing process is minimized, which is crucial to produce thermolabile drugs. However, it is worth noting that there are some limitations associated with this method. One significant drawback is the limited availability of photocurable resins, restricting the range of materials that can be used. Additionally, the process requires a photo initiator to induce photopolymerization, adding an extra requirement to the printing process (31, 46, 48). Many studies have been conducted demonstrating how SLA technology can be useful in the pharmaceutics industry, like the production of modified release tablets (46), 3D printed implants (49), 3D printed hydrogels (31) and 3D printed microneedle patches (48).

Figure 3 Schematic Representation of Stereolithography

SLS technology was invented by Carl Deckard and Joe Beaman in 1984 (50). It is one of the latest and most advanced technologies for the preparation of solid dosage forms. In this process, 3D objects are built by the fusion of powder particles which are selectively heated by the laser. SLS is a manufacturing process involving a laser to selectively sinter the powder particles layer by layer to form the 3D object. The SLS printer consists of a powder bed, powder reservoir, and roller with a laser source. The powder containing drug and polymer is loaded in the powder reservoir and is spread evenly on the power bed from the powder reservoir by the roller. Depending on the design of the object in the CAD file, the laser is directed to draw a specific defined pattern on the surface of the power bed and sinters the powder particles. After the first layer of the object is sintered, the powder bed moves downwards and the powder reservoir moves upwards so that another layer of the powder can be distributed on top of the first layer, and hence printing the object layer by layer which can be recovered from the powder bed once it cools down (51-53). The pharmaceutical grade polymers commonly used in SLS are polyethylene glycol, kollicoat IR, kollidon VA 64, eudragit, polyvinyl alcohol, ethyl cellulose, hydroxymethyl cellulose (54). In the pharmaceutical field, SLS 3D printing has been recently used to prepare orally disintegrating tablets (55, 56), immediate release tablets (51), drug delivery lattice structures (57) and drug delivery devices (58).

Figure 4 Schematic Representation of Selective Laser Sintering

In SLS technology, a variety of parameters are involved in the printing process. Table 2 provides a description of the various process parameters used in SLS 3D printing.