Three-dimensional (3D) printing plays very significant role in pharmaceutical product development to demise many problems of conventional unit operations for pharmaceuticals. The 3D printing technology for pharmaceutical dosage form depends on computer-aided designs. Three-dimensional printing technology is expected to play a crucial role toward biomedical applications. However, 3D printing technology has yet to prove its anticipated benefits and applications.
Three-dimensional printing (additive manufacturing), relate to processes in which material is solidified or joined under computer control to fabricate a 3D object. 3D printing technology for pharmaceutical dosage form like tablets depends on computer-aided designs to attain unique flexibility, particular manufacturing capability and time-saving. The operation involves rapid prototyping of layer by layer fabrication that uses powder processing and liquid binding materials to develop drug materials into the desirable dosage form. 3D printing is expanding its horizon in pharmaceutical product development as an impressive strategy to defeat many challenges of conventional pharmaceutical unit operations. The efforts in developing three-dimensional printing in pharmaceutical product development resulted in a landmark approval by the US FDA of SPRITAM levetiracetam tablets. SPRITAM tablets for oral suspension are unitary porous structures produced by a 3D printing process that binds the powders without compression. For tablets, the conventional pharmaceutical manufacturing unit operation involves milling, mixing, granulation and compression. This may have disparate impact on the quality of final product with respect to drug loading, drug release, drug stability and drug product stability. 3D printing technology has numerous anticipated benefits that still to be proven and require investment of money, time and long lasting vision to evolve into the expected applications. Compared to conventional pharmaceutical product manufacturing process, three-dimensional printing offers high production rates, fast operating systems, high drug-loading, precision, accuracy, material wastage reduction, cost saving and amenability to cover wide range of active pharmaceutical ingredients. Active pharmaceutical ingredients including narrow therapeutic windows drugs, potent drugs, poorly water-soluble drugs, peptides and proteins can be fabricated using three-dimensional printing.
There are different types of 3D printing technologies used in pharmaceuticals. These technologies are Inkjet printing, Direct-write, ZipDose, Thermal Inkjet printing and Fused deposition modelling. In Inkjet printing technique, various combinations of drugs and excipients (ink) are sprayed in tiny droplets in varying sizes layer by layer to form a non-powder substrate. The technique includes powder-based 3D printing that uses a powder substrate for the sprayed ink where it solidifies to form a solid dosage form. Direct-write technique uses a computer controlled translational stage which moves a pattern-generating device in order to accomplish, layer-by-layer, three-dimensional structure. ZipDose Technology use an aqueous fluid to bind multiple layers of powder blend to create a porous and water soluble matrix that disintegrate rapidly with a sip of liquid. ZipDose Technology is developed by Aprecia Pharmaceuticals which is unique delivery platform for orodispersible formulations of highly prescribed, high-dose medications. Thermal Inkjet printing system comprises a micro-resistor that heats a thin film of ink fluid forming small air bubbles in the print-head collapse to provide pressure to eject ink drops. Thermal Inkjet printing provides the opportunity of dispensing extemporaneous preparation or solution of drug onto three-dimensional scaffolds. Fused deposition modelling process applied to dosage forms that apply polymers as a part of the framework like implants, controlled release tablets, bi/tri/multi-layered tablets and fast dissolving tablets or devices. In the process the polymer is melted and extruded through a movable heated nozzle. The layer by layer ejection of the polymer is repeated along x-y-z stage, followed by solidification to form 3D object designed by the computer aided design models.
One of the major concerns is securing approval from respective regulators. Fulfilling regulatory requirements could be an obstacle that may affect the availability of three-dimensional printed pharmaceutical or medical products on a large scale. For instance, the demand for large randomized controlled trials, which may require time and financial support, could present an obstacle to the 3D printed pharmaceutical dosage forms availability. Moreover, regulations for manufacturing and legal requirements from state/country could be barrier for 3D printed pharmaceuticals. As conventional equipments, three-dimensional printers for pharmaceutical dosage forms must be legally defined as equipment for manufacturing. Awareness programs this legal requirement related to three-dimensional printing should be provided by regulator from time to time for the emerging three-dimensional printing technology for pharmaceuticals.
Three-dimensional printing technology is anticipated to play a crucial role toward personalized medicine for customizing drugs, organs, and nutritional products. The bio-printing of complex organs (e.g. heart, kidney) or heterogeneous tissues (e.g. liver and kidney tissues) by the modern 3D printing technology is anticipated to become upcoming revolution. This will also open the window to fabricate models for viable live implants, tissue and organ for use in drug discovery. It might be possible in future to print out a tissue of patient as a strip to find out effectiveness of medication. Stem cells from a child’s baby teeth may be used as a tool kit in the future for developing and growing replacement tissues and organs. In situ bio-printing, of implants or living organs are directly printed in the human body during ongoing operations, is one more anticipated future. In situ bio-printing for repairing external organs (e.g. skin) has already taken place.
Pharmaceutical 3D printing technology has yet to prove its anticipated benefits and applications. So it requires investment of time and money to evolve. Pharmaceutical drug research and development could be improved drastically by three-dimensional printing. Rather than printing objects made out of plastic or metal, imagine printing pills or human organs and tissue. New possibilities in three-dimensional printing may open up a whole new chapter of opportunities for pharmaceutical research and bio-technology applications.
(Author is research scientist, Formulation and Development Department, Gowrie Research Pvt Ltd, Vadodara, Gujarat)