3D printing technology, since its introduction in the 1980s, has transformed various industries. Its ability to rapidly produce complex objects has now captured the attention of pharmaceutical innovators, with the first 3D-printed oral suspension tablet, SPRITAM, approved by the FDA in 2015 for epilepsy treatment. This advancement is paving the way for personalized medicine, offering customized drug formulations in terms of size, shape, release profile, and dose.
Benefits of 3D Printing in Pharmaceuticals
The technique involves depositing materials layer-by-layer based on computer-aided designs. While clinical trials for 3D-printed treatments, such as those for gastric retention, are underway, the global 3D-printed drugs market is projected to grow at a compound annual growth rate of 16% between 2023 and 2031, reaching $322.91 million.
3D printing offers flexibility and precision over traditional manufacturing methods, enabling the development of various dosage formats, including tablets, capsules, and films. Tailored drug release profiles, including immediate- and controlled-release formulations, can be achieved more easily.
One key advantage is the ability to combine previously incompatible active pharmaceutical ingredients (APIs) into a single pill, known as a polypill. This is particularly beneficial for complex conditions like metabolic syndrome, which requires tailored treatment regimens addressing insulin resistance, hypertension, dyslipidemia, type 2 diabetes, obesity, inflammation, and non-alcoholic fatty liver disease.
Case Studies and Applications
In a recent study, researchers manufactured a polypill using fused deposition modeling, containing nifedipine (antihypertensive), simvastatin (antihyperlipidemic), and gliclazide (antihyperglycemic) to address hypertension, dyslipidemia, and type 2 diabetes, respectively. The polypill exhibited a dual-release profile, with fast release for simvastatin and sustained release for nifedipine and gliclazide. However, further studies are needed to optimize excipient selection for clinical use.
Another study demonstrated the use of 3D printing for delivering challenging APIs, such as the thermo-sensitive anti-cancer drug 5-fluorouracil (5FU). Researchers created 3D-printed oral tablets loaded with 5FU, demonstrating good flow properties, porous texture, and homogenous drug distribution. The drug dose, release rate, and tablet shape and size could be adjusted by optimizing the composition of the powder bed with pharmaceutical-grade excipients. Similarly, 3D printing can improve the bioavailability of poorly soluble drugs like domperidone, an anti-sickness medicine. A fused deposition model was used to create a 3D-printed domperidone tablet with a hollow structure, increasing absorption and bioavailability in an animal model.
Role of Excipients
Excipients are crucial in 3D printing, contributing to viscosity, rheology, flow properties, structural integrity, and overall functionality. Hydroxypropyl methylcellulose (HPMC), for example, is a biodegradable polymer that can be used in various 3D printing techniques to achieve immediate-release or modified-release profiles.
For immediate-release, HPMC can be used as a substrate in printer-based inkjet techniques. Studies have shown that the viscosity of HPMC affects the physical and mechanical properties of the substrate, impacting drug release. High viscosity HPMC is best for creating and retaining a porous structure.
In modified-release formulations, high viscosity HPMC can be used as a controlled-release polymer, combined with low viscosity HPMC as a binding agent to create 3D-printed bilayer and polypill tablets. Additionally, 3D-printed non-effervescent gastric floating tablets can be produced using the inkjet printing technique with different viscosity grades of HPMC, supporting sustained drug release in the stomach.
Nozzle-based deposition systems also benefit from HPMC, where the viscosity of HPMC can impact the drug release profile. As viscosity increases, filament strength increases, while drug release from the printed tablet decreases.
Challenges and Considerations
Despite the potential, several factors must be considered for the widespread adoption of 3D printing in pharmaceuticals:
- Regulatory Requirements: The regulatory landscape for 3D-printed drugs is not well-defined in Europe, China, or the US. Drug developers must conduct thorough due diligence to identify potential regulatory hurdles.
- Quality Control: Ensuring quality is a significant challenge. Manufacturers must implement stringent quality control measures throughout the 3D printing process, including sourcing raw materials from reputable suppliers.
- Cost Considerations: 3D printing currently favors small-scale production and may not be economically viable for mass manufacturing. However, it offers cost-saving advantages for on-demand manufacturing, such as minimal raw material waste and customization without time-consuming manufacturing changes.
- Excipient Selection: Choosing the most suitable excipient is crucial for achieving the desired functions and overall performance of a printed solid oral dosage form.
