Selective Laser Sintering for printing pharmaceutical dosage forms
Abstract
Three-dimensional (3D) printing has revolutionised the field of pharmaceutical manufacturing due to the unique capabilities to tailor the dosage forms properties and overcome constrains of conventional technologies. There is a plurality of 3D printing techniques that offer flexibility on the shape, geometry, active(s) dose and dissolution rates for improved patient treatment. Over the last few years selective laser sintering (SLS) has captured research interest for the development of innovative drug products. SLS possess technological features that can transform medicine manufacturing from one-size-fits-all to personalised dosage forms with improved clinical outcomes, patient acceptability, and adherence. Moreover, SLS has the capacity to pave the way for decentralised manufacturing and introduce new supply chain models with reduce complexity. In this review we present the technological features, manufacturing challenges, advantages and limitations of SLS for manufacturing medicines.
Introduction
Three-dimensional printing (3DP) has gained increasing popularity over the last 10 years in healthcare due to its enormous capability for resolving several of the limitations associated with conventional drug delivery and therapeutic technologies [[1], [2], [3]]. Binder jetting, fused deposition modelling (FDM), powder bed fusion (PBF), and vat polymerization are just a few of the printing technologies that have been developed and employed in the pharmaceutical and biomedical industries throughout the years. Around 1981, Hideo Kodama developed a method for creating 3D models using photo-hardening polymers and UV radiation [4]. A few years later, Chuck W. Hull created the first 3D printing technology, stereolithography, which was marketed by 3D systems [5]. Initially, these technologies were limited in their application due to poor printing quality and excessive costs. Nevertheless, technological breakthroughs have resulted in the development of cost-effective, high-print-speed, and high-precision 3D printers that have already been employed in a multitude of sectors including biomedical, space, education, automotive, and art over the last two decades.
In recent years, considerable technological advancements (Fig. 1), resulted in the development of Spritam®, an antiepileptic drug, the first commercially available 3D-printed oral medication approved by the FDA (Food and Drug Administration) in 2015. Two years later, FDA produced the “Technical Considerations for Additive Manufactured Medical Devices,” a guide for industry and FDA employees while research in 3D printed medicines continues [6].
3D printing or additive manufacturing refers to the fabrication of three-dimensional (3D) object from a computer-aided design (CAD), in a layer-by-layer manner. The CAD file is converted into a stereolithography file (.stl file) that contains the necessary information for the spatial geometry of the object to be produced using CAD programmes. The.stl file is divided into multiple segments after initiation, one of which is the slice file (SLI segment), which is subsequently transferred to the 3D printer for printing. Most of the 3D printing technologies have the capacity to transform the pharmaceutical sector from one-fit-for-all tablet and capsule mass manufacturing to customised dosage forms that fit the clinical needs of the patients [7].
Since the introduction of 3D printing with stereolithography, various more techniques have been established (Fig. 2), allowing for the processing of a broader range of materials, such as polymers, metals, and ceramics. Nanomaterials, medicines, and biological materials like cells can all be included into 3D constructions, opening a whole new world of possibilities for medical 3D printing.
Extrusion-based technologies, such as FDM, are by far the most extensively used 3D printing technology. The technology was invented by Scott Crump, Stratasys’ co-founder, and patented in 1989 [8]. An FDM printer system (Fig. 2c) comprises of a feeder gear system that enables material to be driven through the system, a heated liquefier that is located in the print head and is a system for making the material extrudable, the print head and nozzle, the printer’s axels that allow the print head to move following cartesian patterns, and finally the build platform. In this process, layers of molten or softened thermoplastic materials in the form of filament are deposited via the printer’s head at specified directions controlled by the computer software for the fabrication of the designed structure. In comparison to other 3D printing technologies, FDM is comparatively inexpensive, and has been successfully implemented in a variety of industries [[9], [10], [11]].
Material Jetting (MJ), also known as Poly-jetting, and Drop on Demand (DoD) are two other type of 3D printing technologies that have been used for the manufacturing of medical devices and pharmaceutical dosage forms (Fig. 2e and f). These technologies deposit similarly to a typical inkjet printer, but the object is formed by stacking numerous layers of material on top of each other. Both MJ and DoD deposit very small polymer droplets, but MJ applies UV irradiation to cure separately each layer after deposition. In contrast, DoD uses wax-like substances that solidify quickly, while a fly cutter passes the build area after the deposition of each layer to minimize wastage. Binder Jetting technologies (Fig. 2d) fuse sequential layers of each cross-section layer using a low viscosity liquid binder. The layer is formed, and the next layer of powdered material is prepared for the deposition of liquid binder in a similar way to PBF processes. The post processing includes the removal of loose powder and infiltration of the layered structure with a liquid such as an epoxy resin, to help build strength and improve appearance.
Table 1: Pharmaceutical grade polymers suitable for SLS applications
| Polymers | Chemical name | Dissolution properties | Tg (°C) |
|---|---|---|---|
| Kollidon VA64 | Vinylpyrrolidone-vinyl acetate copolymer | Immediate release | 106.0 |
| Kollicoat IR | Polyethylene glycolpolyvinyl alcohol graft copolymer | Immediate release | 69.7 |
| Plasdone S630 | Copolymer of N-vinyl-2- pyrrolidone and vinyl acetate | Immediate release | 109.0 |
| Eudragit EPO | Cationic N,Ndimethylaminoethyl methacrylate copolymer | Immediate release up to pH 5.0 | 46.0 |
| Eudragit RLPO | ethyl acrylate, methyl methacrylate copolymer | Sustained release (highly permeable) | 70.0 |
| Eudragit L100-55 | Anionic methacrylic acid - methyl methacrylate copolymer | Dissolution above pH 6.0 | 150.0 |
| Eudragit S100 | Anionic metacrylic acid and methyl metacrylate coplymer | Dissolution above pH 7.0 | 150.0 |
| ETHOCEL N7 | Ethylcellulose (nonionic) | Sustained release | 106.0 |
| Soluplus | Polyvinyl caprolactampolyvinyl acetate-polyethylene glycol graft co-polymer | Immediate release | 70.0 |
| AQOAT ASHMP/LMP/MMP | Hydroxypropyl methylcellulose acetate succinate | Dissolution above pH 5.5, 6.0, 6.5 | 120.0 |
| HPMC (15LV, 4M, 100LV) | Hydroxypropyl Methylcellulose | Immediate/Controlled release | 120.0 |
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Excipients mentioned in the study: Kollicoat, Eudragit L100-55, Kollidon VA64, Eudragit EPO, Plasdone 630
Atabak Ghanizadeh Tabriz, Hannah Kuofie, James Scoble, Sam Boulton, Dennis Douroumis, Selective Laser Sintering for printing pharmaceutical dosage forms, Journal of Drug Delivery Science and Technology, 2023, 104699, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2023.104699.
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