3D Printing: A Formula for Success in Drug Development and Personalized Medicine

Figure1. Timeline of 3D printing

The hands-on application of additive manufacturing is commonly referred to as rapid prototyping. Rapid prototyping supports iterative design improvements, as modifications can be easily incorporated into updated digital models and reproduced without the need for costly tooling. As a result, it accelerates product development cycles, enhances innovation, and bridges the gap between conceptual design and full-scale manufacturing across various scientific and industrial domains⁴. In 2015, the U.S. Food and Drug Administration approved SPRITAM®, the first commercially available drug product manufactured using three-dimensional printing technology. This landmark approval marked the beginning of a new era in pharmaceutical manufacturing, often referred to as pharmaco-printing. Consequently, the FDA approval of SPRITAM® served as a catalyst for innovation, paving the way for the integration of advanced manufacturing technologies into modern pharmaceutical development⁵. Integrating three-dimensional (3D) printing into healthcare environments has the potential to fundamentally transform clinical pharmacy practice. By shifting drug production closer to the point of care, this technology enables pharmacists to move beyond conventional, mass-manufactured medicines toward more flexible and patient-centric solutions.The adaptability of 3D printing also supports timely modification of therapy in response to changing clinical conditions, improving medication adherence and therapeutic outcomes⁶. Beyond improving patient adherence and overcoming logistical constraints, this approach offers promising economic advantages. The capability to manufacture medicines on demand enables a shift away from centralized, large-scale production and extensive inventory maintenance. By minimizing dependence on bulk manufacturing, long-term storage, and complex supply chains, wastage due to expiration or overproduction can be significantly reduced. Furthermore, localized and need-based drug fabrication may lower transportation and distribution expenses, ultimately contributing to a more efficient and cost-effective healthcare system over time⁷. Three-dimensional (3D) printing technologies have emerged as versatile tools in pharmaceutical manufacturing, enabling the fabrication of a wide spectrum of drug delivery systems. Using layer-by-layer deposition, this technology has been successfully applied to produce immediate-release and modified-release tablets with precisely controlled drug doses and release profiles⁸. In addition, 3D printing allows the development of fast-dissolving oral films and dispersible dosage forms, which are particularly beneficial for pediatric, geriatric, and dysphagic patients⁹. Beyond oral dosage forms, 3D printing has expanded into advanced therapeutic platforms such as microneedle arrays for painless and minimally invasive drug delivery, customized implants with complex geometries for sustained local therapy, and transdermal patches designed for controlled and prolonged drug permeation through the skin. The ability to tailor shape, size, porosity, and drug distribution within a single dosage form highlights the potential of 3D printing to support personalized medicine, enhance patient adherence, and improve therapeutic outcomes¹⁰.

Figure2. 3D Printing in personalized treatment

MECHANISM OF 3D PRINTING:

1. Design:

• 3D Modeling: The process starts with creating a digital 3D model using CAD
• (Computer-Aided Design) software. This model defines the shape and dimensions of the object¹¹.
• Slicing: The model is then sliced into thin horizontal layers using slicing software. This creates a set of instructions (G-code) for the printer to follow¹¹.

2. Preparation:

• Material Selection: Various materials can be used for 3D printing, including plastics (like PLA and ABS), metals, ceramics, and even biological materials¹².
• Printer Setup: The 3D printer is prepared, including loading the material and  calibrating settings such as temperature and print speed.

3. Printing Process:

• Layer-by-Layer Construction: The printer deposits or solidifies material layer by  layer according to the G-code¹¹. Common methods include:

1. Fused Deposition Modeling (FDM): Melting and extruding thermoplastic filament.
2. Stereolithography (SLA): Using a laser to cure liquid resin into solid layers.
3. Selective Laser Sintering (SLS): Fusing powdered material using a laser.

4. Post-Processing :

After printing, the object often requires finishing touches¹³.

5. Final Product

The completed object is a precise replica of the digital model, often used for prototyping, manufacturing, or customized products¹¹.

Figure3. Working mechanism of 3d printing technology

Types of 3D Printing Techniques:

1. Fused Deposition Modeling (FDM):

• Overview:

Fused Deposition Modeling (FDM) is one of the most widely used 3D printing techniques due to its simplicity and cost-effectiveness. It works by extruding a thermoplastic filament, which is melted and deposited layer by layer onto a substrate to create a three-dimensional structure¹⁴.

• Application in Pharmaceuticals:

In drug manufacturing, FDM is used to create solid oral dosage forms, such as tablets, sustained release capsule shaped tablets of theophylline were developed¹⁵. Drug-laden filaments can be prepared by mixing active pharmaceutical ingredients (APIs) with a polymeric matrix. These filaments are then fed into the FDM printer, which builds customized tablets by adjusting the drug's composition, dosage, and release characteristics. Fabrication of microneedle-based systems for minimally invasive and controlled drug delivery¹⁶. In dentistry, drug-incorporated orthodontic retainers have been developed to provide sustained local therapeutic effects while maintaining patient comfort and compliance¹⁷. Additionally, 3D-printed topical facial masks embedded with active pharmaceutical ingredients offer targeted and uniform drug deposition on the skin surface¹⁸. In the field of women’s health, drug-loaded vaginal rings produced via advanced manufacturing techniques enable prolonged and localized drug release, improving therapeutic efficacy and reducing systemic side effects¹⁹.

• Advantages:

Customizable drug release profiles, ability to combine multiple APIs in a single tablet, and potential for rapid production of small batches.

• Limitations:

The need for thermally stable drugs, as high temperatures are required to melt the polymers, and limited resolution compared to other techniques.

2. Stereolithography (SLA):

• Overview:

Stereolithography (SLA) uses a liquid resin that is cured layer by layer using a UV laser. The laser selectively solidifies the resin in specific areas, gradually building up the desired 3D object²⁰.

• Application in Pharmaceuticals:

SLA is particularly useful for creating highly accurate drug delivery devices and implants. It allows for precise control over the geometry and porosity of the printed structures, making it suitable for producing complex and intricate drug delivery systems. Ascorbic acid–loaded solid hydrogel dosage forms were fabricated using poly(ethylene glycol) dimethacrylate, with riboflavin serving as a biocompatible photoinitiator. This system enabled uniform drug incorporation and stable crosslinked structures, demonstrating potential for controlled drug delivery applications²¹. Microreservoir-based systems for implantable and transdermal drug delivery were successfully fabricated using stereolithography (SLA) technology. The high printing resolution offered by SLA enabled precise control over reservoir geometry and dimensions, facilitating accurate drug loading and predictable release profiles²².

• Advantages:

High resolution, ability to create intricate designs, and suitability for making implants and sustained-release systems.

• Limitations:

Limited material selection (photosensitive resins) and the potential for residual photoinitiators, which could pose toxicity concerns in pharmaceutical applications.

3. Selective Laser Sintering (SLS):

• Overview:

Selective Laser Sintering (SLS) involves the use of a laser to selectively fuse powdered materials into a solid structure²³. The laser sinters (heats without melting) specific regions of the powder bed, layer by layer, until the desired object is formed²⁴.

• Application in Pharmaceuticals:

SLS has shown promise in fabricating drug-loaded structures, particularly for sustained-release formulations. By adjusting the porosity of the printed object, the release kinetics of the drug can be controlled. This technique also supports the production of personalized dosage forms. Orally disintegrating printlets containing paracetamol were successfully fabricated using polymeric carriers such as hydroxypropyl methylcellulose (HPMC) and Kollidon, enabling rapid tablet disintegration and improved patient convenience²⁵. In a separate approach, ondansetron printlets were produced following drug–cyclodextrin complexation, with mannitol and Kollidon incorporated to enhance drug stability, taste masking, and dissolution performance²⁶. Additionally, mini-printlet formulations combining paracetamol and ibuprofen were explored, allowing tailored and programmable drug release profiles to be achieved within a single dosage unit²⁷. Beyond conventional tablet geometries, paracetamol-loaded gyroid structures were designed using polymers including polyethylene oxide, Eudragit, and ethyl cellulose, demonstrating how complex internal architectures and polymer selection can be strategically employed to modulate drug release kinetics²⁸.

• Advantages:

No need for a binder or solvent, high precision, and the ability to produce complex structures with controlled porosity.

• Limitations:

Limited range of printable pharmaceutical excipients and potential degradation of heat-sensitive APIs.

4. Inkjet Printing (Binder Jetting):

• Overview:

Inkjet printing, also known as binder jetting, involves the deposition of droplets of liquid binder onto a powder bed to selectively bind the powder particles together. Layers of powder are added sequentially, and the binder is deposited to form the desired structure²⁹.

• Application in Pharmaceuticals:

Inkjet printing is suitable for creating rapid-dissolving formulations and multilayered dosage forms. It allows for precise control over the spatial distribution of APIs, enabling the production of tablets with multiple drugs that have different release profiles. Binder jetting has been widely investigated for tablet fabrication, with excipient type and concentration playing a key role in determining tablet properties. Highly water-soluble fillers, high-moisture wetting agents, and viscous binders have been shown to improve tablet hardness and binding strength while prolonging disintegration time³⁰. Amitriptyline hydrochloride–containing dosage forms were successfully developed using binder jetting technology. This approach enabled precise deposition of the binder solution and uniform drug distribution within the printed tablets, allowing effective control over tablet structure, mechanical strength, and drug release behavior. The study demonstrates the potential of binder jetting as a versatile platform for fabricating personalized oral dosage forms of amitriptyline hydrochloride³¹.

• Advantages:

High precision, flexibility in formulation, ability to print multilayer tablets, and potential for creating personalized medicine.

• Limitations:

Limited range of printable materials and challenges with printing viscous liquids.

5. Powder Bed Fusion (PBF):

• Overview:

Powder Bed Fusion (PBF) is a technique that uses a heat source (usually a laser or electron beam) to fuse particles in a powder bed layer by layer. This method is similar to SLS but allows for a broader range of materials to be processed ³².

• Application in Pharmaceuticals:

PBF is used for creating complex, highly porous drug delivery systems, such as implants or scaffolds for tissue engineering. It enables the fabrication of structures with controlled drug release properties and the incorporation of multiple drugs into a single device. Paracetamol and indomethacin successfully processed without significant degradation. Beyond tablets, PBF is expanding into drug-eluting medical devices, antibiotic-loaded implants for bone infection treatment³³.

• Advantages:

Ability to create porous structures, controlled drug release, and versatility in material selection.

• Limitations:

Potential degradation of heat-sensitive drugs and limited use in oral dosage form production.

6. Semi-Solid Extrusion (SSE):

• Overview:

Semi-Solid Extrusion (SSE) involves the use of a semi-solid paste, which is extruded through a nozzle to build up layers and create a three-dimensional object. This technique allows for the incorporation of drugs into a paste-like formulation, which is then shaped into a specific dosage form.

• Application in Pharmaceuticals:

SSE is particularly useful for creating personalized tablets and drug delivery systems with complex geometries. It allows for the precise positioning of drugs within the structure, enabling controlled release profiles. Semi-solid extrusion (SSE) 3D printing was first translated into clinical practice for the on-site manufacture of patient-specific printlets in a hospital pharmacy. In this work, chewable dosage forms with customised flavours and colours were produced on demand and administered to paediatric patients suffering from a rare metabolic condition. Preference studies showed that children favoured chewable printlets over formulations produced using other 3D printing technologies, such as DLP, SLS and FDM. While printlets fabricated by DLP and SLS were initially perceived as more visually appealing, awareness of the chewable nature of the SSE printlets led most children to ultimately select them as their preferred dosage form³⁴.

• Advantages:

Flexibility in formulations, compatibility with a wide range of drugs, and the ability to create complex, personalized dosage forms.

• Limitations:

Limited to semi-solid formulations and challenges with maintaining stability during the extrusion process.

7. Hot-Melt Extrusion (HME):

• Overview:

Hot-Melt Extrusion (HME) is a technique that involves heating a polymer-based formulation until it becomes a molten semi-solid, which is then extruded through a nozzle to create 3D structures. The extruded material solidifies upon cooling.

• Application in Pharmaceuticals:

HME is widely used to produce sustained-release dosage forms, drug-loaded implants, and filaments for FDM 3D printers. It allows for the incorporation of APIs into polymers that can modulate drug release. Hot-melt extrusion (HME) is widely used to produce solid dispersions that enhance drug solubility and bioavailability by uniformly distributing the API within polymeric or lipid carriers³⁵.

• Advantages:

Suitable for controlled-release formulations, high drug loading capacity, and compatibility with thermally stable APIs.

• Limitations:

High processing temperatures, which may degrade heat-sensitive drugs, and limited flexibility in the choice of materials.

Figure4. Types of 3D printing techniques

Advantages of 3D Printing^36,37:

1. Personalisation of dosage forms:

3D printing enables precise tailoring of drug dose, size, shape, and drug release profile according to individual patient needs, overcoming the limitations of conventional “one-dose-fits-all” manufacturing.

2. High dosing accuracy and reproducibility:

Computer-controlled fabrication allows accurate placement of drug and excipients, resulting in excellent content uniformity and reduced dose variability, even for low-dose drugs.

3. Design flexibility and complex geometries:

Unlike traditional manufacturing, 3D printing can fabricate complex internal structures (porous matrices, multilayered systems, hollow designs), enabling controlled and programmable drug release behaviour.

4. Rapid prototyping and reduced development time:

Formulations can be designed, modified, and produced quickly without the need for expensive tooling, significantly shortening formulation development and optimisation timelines.

5. On-demand and decentralized manufacturing:

3D printing supports point-of-care and on-demand drug production, reducing reliance on large-scale batch manufacturing, storage, and supply chain constraints.

6. Improved patient compliance:

Customised dosage forms with optimised size, shape, taste, and dosing frequency can enhance patient acceptability and adherence, especially in paediatric and geriatric populations.

7. Capability for multi-drug incorporation:

Multiple drugs with different release profiles can be integrated into a single dosage form, enabling simplified therapy and reduced pill burden.

8. Material efficiency and reduced waste:

Additive manufacturing deposits material layer-by-layer only where required, minimising raw material wastage compared to subtractive manufacturing processes.

9. Facilitation of innovative dosage form design:

The technology enables novel pharmaceutical concepts that are not feasible using conventional methods, fostering innovation in dosage form engineering and drug delivery science.

Disadvantages of 3D Printing^38,39,40:

1. Regulatory uncertainty and lack of standardized guidelines:

Existing pharmaceutical regulations are designed for batch manufacturing, not on-demand or patient-specific production. This creates ambiguity in approval pathways, quality assurance, and post-marketing surveillance for 3D-printed dosage forms.

2. Challenges in ensuring batch-to-batch and unit-to-unit uniformity:

Even small variations in printing parameters (temperature, feed rate, layer height) can significantly affect dose accuracy, mechanical strength, and drug release, making reproducibility difficult compared to conventional manufacturing.

3. Limited availability of pharmaceutically acceptable printable materials:

Only a narrow range of polymers and excipients possess suitable printability, stability, and regulatory acceptance, restricting formulation flexibility and drug compatibility.

4. Thermal and mechanical stress on active pharmaceutical ingredients (APIs):

Many 3D printing techniques involve high temperatures or shear forces, which may cause degradation of thermolabile or shear-sensitive drugs, limiting the range of APIs that can be safely processed.

5. High initial investment and operational costs:

Specialized printers, software, maintenance, and trained personnel increase capital and operational expenditure, making large-scale adoption economically challenging, particularly in low-resource settings.

6. Post-processing requirements:

Additional steps such as drying, curing, or removal of support materials can affect drug stability and increase processing time, complexity, and risk of variability.

7. Data security and intellectual property concerns:

Digital design files used in 3D printing are vulnerable to unauthorized access, modification, or replication, posing risks to patient safety and intellectual property protection.

8. Integration challenges within existing pharmaceutical supply chains:

Implementing 3D printing requires significant changes in manufacturing workflows, quality systems, and distribution models, which can be difficult for established pharmaceutical industries to adopt.

3D PRINTING IN PERSONALIZED MEDICINE:

1. Personalization of drug dose:

Patient responses to drug therapy vary due to differences in age, genetics, and biological markers, necessitating personalized dosing strategies. Three-dimensional printing enables precise, individualized dose adjustment by digitally modifying the size and geometry of dosage forms, thereby eliminating inaccuracies associated with tablet splitting. This capability has been demonstrated by the fabrication of theophylline tablets with doses ranging from 60–300 mg and by the production of spironolactone and hydrochlorothiazide tablets in which dose was linearly correlated with tablet volume. These studies confirmed high dose accuracy, pharmacopoeial compliance, and strong acceptance of 3D-printed personalized medicines in clinical practice⁴¹.

2. Regulation of drug release:

Drug release can be personalized using 3D printing by modifying the tablet’s geometry, polymer type, and internal structure to achieve immediate, sustained, delayed, or pulsatile release. For example, HPMC–diltiazem tablets with varied infill and design patterns, demonstrating in vivo pharmacokinetics matching in vitro release were studied. Some studies have highlighted the role of tablet size, drug loading, and surface area-to-volume ratio in controlling release kinetics. Wen et al. combined gastro-retention with zero-order release for 10–12 hours⁴², while Gioumouxouzis et al. developed pH-responsive colon-targeted  tablets, showing release profiles can be precisely tailored through design⁴³.

3. Personalized treatment for pediatrics:

Pediatric patients require special consideration in pharmacotherapy due to the need for safe and effective treatments. Pediatric dosage forms are limited and must meet strict criteria regarding dose accuracy, toxicity, and organoleptic properties. Dosing should be carefully determined based on age, development, and body characteristics, and all components, including active ingredients and excipients, must be evaluated for potential toxicity in children. Ease of administration and taste are particularly important, as children are more sensitive to bitter flavors than adults⁴⁴. Common pediatric formulations include oral solutions, suspensions, orodispersible films, powders, and tablets (small, scored, chewable, or mini/orodispersible tablets)⁴⁵. 3D printing is emerging as a tool for personalized pediatric medications, allowing customization of shape and color while supporting safe and effective delivery. Additionally, it offers a solution for children with swallowing difficulties by enabling the production of orodispersible films, tablets, and chewable forms⁴⁶.

Figure5. 3D printed gummies for pediatrics⁴⁷.

4. Personalized treatment for geriatrics:

The geriatric population often faces multiple health conditions and challenges such as variable drug responses, difficulty swallowing, and trouble managing medications (e.g., pill splitting), highlighting the need for personalized medicine⁴⁸. Polypharmacy, the use of multiple medications by a single patient, often reduces adherence and increases the risk of adverse effects and drug interactions ⁴⁹. 3D printing provides a potential solution through polypills—single tablets combining multiple drugs tailored to an individual’s therapeutic needs. For example, Khaled et al. developed a 3D-printed polypill with three drugs in separate compartments for controlled release, aimed at hypertensive diabetic patients⁵⁰. Other studies have created polypills containing four to six drugs for cardiovascular therapy, while some have explored personalized supplementation. Patient preferences are critical for acceptability. Fasto et al. found that polypharmacy patients generally favor conventional tablet shapes, though color and design choices vary individually. Polypills are well-received because they reduce the number of tablets taken daily⁵¹.

Figure6. 3D printed tablets in various shapes,  3D printed polypills with different number of compartments( lower)^50,51.

5. Personalized treatment for visually impaired:

Visually impaired patients often face challenges in medication use, particularly in identifying and differentiating drugs once packaging is removed or altered. Three-dimensional (3D) printing enables the direct incorporation of tactile identifiers onto dosage forms, offering a practical solution to this issue. For example, orally disintegrating tablets embedded with Braille and Moon characters have been fabricated to convey information such as drug indication or dose, and their legibility was successfully confirmed by a visually impaired volunteer⁵². In another approach, 3D-printed intraoral films containing raised Braille text were developed for personalized therapy; in vivo haptic evaluations by recruited volunteers verified the clarity of the tactile characters and demonstrated the potential of 3D printing to enhance medication accessibility for visually impaired patients⁵³.

Figure7. 3D printed tablets with Braille and moon characters for visually impaired, intraoral films^52,53.