The use of three-dimensional objects is nothing new in human history such as in the areas of food, fashion, toys, automobiles, constructions and needless to mention in pharmaceuticals. The oldest known pills can be traced back to 140 BC and the first compressed tablets were prepared by Dr. Robert Fuller in 1878. 3D printing can be used to print anything that is sketched in 3D as it requires a CAD file, or a 3D digital model. The first 3D printer was developed by Charles Hull in 1984, and since then different applications of this technology have been applied to several industries.
Three-dimensional (3D) printing is a very recent innovation in pharmaceutical formulation that has emerged as one of the most revolutionary and powerful tools towards personalized medicine. The first 3D printed object was a tiny cup for eye wash invented by Chuck Hill in 1984. The first 3D pill in Pharmaceutical has been reported in 1996. A 3D printed human skull was successfully implanted in a 22-year-old woman in Netherlands in 2014 and 3D printer-created human ear, kidney, liver and heart are being used successfully for many years. The ﬁrst orally disintegrating 3D printed tablet, Spritam® (levetiracetam)-an anti-epileptic drug, was approved by U.S. Food and Drug Administration in 2015. Smart manufacturers are constantly investing in 3D-printing research, while new entrepreneurs are also breaking into the pharmaceutical space.
Precision medicine is one of the major areas where 3D printing technology can bring about a revolution. In recent years, patient-centric dosage form design is a noticeable trend in pharmaceutical formulation. Pharmaceutical formulation scientists are constantly motivated towards new concepts in drug design, better understanding of material properties, manufacturing technology and processes that assures the best quality drug products.
Precision medicine is an approach that allows doctors to select treatments that are most likely to help patients based on a genetic understanding of their disease. This relatively new branch of therapy is also known as personalized medicine. Inter-personal variability is an increasingly global problem when treating patients from different socio-economic, cultural and genetic make-ups. Pharmacogenomics uses information about a person's genetic makeup, to choose the drugs that are likely to work best for that particular person. Until recently, drugs have been developed with the idea that each drug works pretty much the same way in every single patient. But genomic research has changed that "one size fits all" approach and opened the door to more personalized approaches to using and developing drugs.
Diseases that are very rare and found in less than 200,000 patients in the United States are known as orphan diseases, which is the cutoff point for the number of patients for a drug to be profitable. Because many thousands of orphan diseases exist in the aggregate (about 20 to 30 million Americans have orphan diseases), these patients are disenfranchised from drug development by the pharmaceutical industries. The orphan diseases are often so rare that a physician may observe only 1 case a year or less. So proper treatment is a personalized encounter between doctor and patient.
Orphan diseases and orphan drugs are most important contributing factors towards the development of personalized therapy and customized dosage forms. 3D printing holds tremendous promise for orphan drugs, designed to treat very small group of patients that are usually not developed by the pharmaceutical industry due to economic reasons. As a result, Orphan drugs currently occupy a large part of personalized medicine. The FDA Office of Orphan Products Development (OOPD) is constantly working to advance the evaluation and development of products (drugs, biologics, devices, or medical foods) that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions.
Three-dimensional (3D) printing is a form of additive manufacturing (AM) programmed with a computer aided design (CAD) wherein a structure is built by depositing or binding materials in successive layers to produce a 3D object. With the simultaneous ascending trend in patient-centric drug product development found within the last decade, 3D printing is now one of the fastest developing branches of technology, art and science.
Advantages of 3D printing over conventional manufacturing:
- Direct digital manufacturing “just in-time” in pharmacy or any healthcare facilities
- Accurate and precise dosing of potent drugs
- Product of different geometric shapes
- Cost-effective because of less manufacturing waste
- Avoiding traditional complex supply chain
- Drug product with customized dosage strength etc.
Among almost 4-decades of 3DP history many different techniques were developed and evolved with technological progress. The main methods are based on powder solidification, liquid solidification, & hot melt extrusion (HME). Hot melt extrusion (HME) as well as extrusion of semisolid materials are still the methods of choice for the formulation of pharmaceutical products. Hot melt extrusion (HME) is the process of melting polymer and drug at high temperature and pressure in the instrument for continuous blending. It is a continuous manufacturing process that includes several operations such as feeding, heating, mixing and shaping. Each 3D printer which works according to a different mode requires sufficient material to be solidified and subsequent object fabrication. Despite of the diversity of 3DP methods, preparation of 3D-printed object in general, includes the following basic steps:
- the design of 3D object with computer-aided drafting (CAD) software and optimization of the geometry according to printer specification;
- the export of 3D model to a common and printer recognizable file format that includes only 3D geometry;
- the import of the file to the software and generation of layers which will be printed;
- the fabrication of the object by subsequent solidification of the material layers.
In conclusion, 3D printing could add a multitude of possibilities to personalized medicine. On demand printing of drug products can be implemented for medicines with limited shelf life or for patient specific medications, offering an alternative to traditional compounding pharmacies. In fact, the technology has opened endless opportunities for the development of personalized medicines and orphan drugs. Despite the unprecedented patient-benefits, this promising method is not completely devoid of drawbacks such as a lack of regulation, safety and security concerns. To overcome the challenges, strict regulatory control and extensive research is necessary to make the technique industrially feasible for drug manufacturing.
L. Srinivas et al., 3D Printing in Pharmaceutical Technology: A Review, Int. Res. J. Pharm. (2019), 10 (2).
S. Anderson. A Brief History of Pharmacy and Pharmaceuticals, Pharmaceutical Press, London, (2005).
3D Printing in Drug Development & Emerging Health Care.
Nayan G. Solanki, Md Tahsin, Ankita V. Shah, Abu T.M. Serajuddin, Journal of Pharmaceutical Sciences 107 (2018), 390-401.
George J. Brewer, Drug development for orphan diseases in the context of personalized medicine, Translational Research 154 (2009), 314-322.
Office of Orphan Products Development.
Witold Jamróz, Joanna Szafraniec, Mateusz Kurek, Renata Jachowicz, Pharm. Res. (2018) 35: 176.
Ahmed Zidan, Alaadin Alayoubi, James Coburn, Sarah Asfari, Bahaa Ghammraoui, CeliaN.Cruza, Muhammad Ashraf, International Journal of Pharmaceutics 554 (2019), 292–301.
FDA’s Role in 3D Printing.
Anna Aimar, Augusto Palermo, Bernardo Innocenti, Journal of Healthcare Engineering (2019).