3D Printing Microstructures for New Drug Delivery Systems with SPHRINT

In the recently published, ‘SPHRINT – Printing Drug Delivery Microspheres from Polymeric Melts,’ authors Tal Shpigel, Almog Uziel, and Dan Y. Lewitus explore better ways to offer sustained release pharmaceuticals via 3D printed structures.

Currently, numerous materials are used to create microparticles for sustained drug release, with numerous choices in biodegradable materials, such as include poly(lactic acid) (PLA), polyglycolic acid (PGA), their copolymer poly(lactic-co-glycolic) acid (PLGA) and polycaprolactone.

“Numerous microparticle-based depots products are FDA approved, amongst them are: Zmax® (Azithromycin), Decapeptyl®/Trelstar® (Triptorelin), Vivitrol® (Naltrexone), Arestin® (Minocycline), Risperdal® Consta® (Risperidone), Sandostatin® LAR Depot (Octreotide), Nutropin Depot® (Somatropin), Lupron Depot® (Leuprolide), DepoCyt® (Cytarabine), DepoDur® (Morphine), Bydureon® (Exenatide) Somatuline LA (Lanreotide) [1] and recently approved ZILRETTA™ (triamcinolone acetonide),” state the authors.

Frames obtained from high-speed imaging capturing the evolution of the shape of a molten 30% IBU-PCL blend interacting with either a superoleophobic
surface (top) and preserving its spherical shape after 1.8 s or an aluminum surface (bottom), in which the droplet gradually flattens (See SI Video 4 and SI Video 5,
respectively). Scale bar: 500 µm. These frames emphasis the significance of using non-wetting surfaces responsible for the formation of spherical droplets.

With the advent of 3D printing and inkjet technology, researchers have experimented with numerous techniques. Many have encountered obstacles though, and challenges regarding methods relying on both inkjet printing and those that are solvent based. Because of that, the researchers created an affordable, yet solvent-free technique for fabricating polymer melts in this study—showing the capability of their SPHRINT technique.

(A) Optical images of (i) neat PCL (154 ± 3°), (ii) 30% IBU-PCL (171 ± 4°), (iii) neat PLGA (167 ± 6°), and (iv) 30% IBU-PLGA (169 ± 4°) microspheres, cooled at room temperature (RT). The values in brackets denote the “sphericity,” expressed as the contact angle values (mean ± S.E.M., n = 10). Scale bar: 200 µm. (B) SEM images of (i) 30% IBU-PCL and (ii) 30% IBU-PLGA microspheres, cooled at RT. Scale bars: 100 µm

Producing drug delivery microspheres from a polymer loaded with a sample drug like ibuprofen, the researchers experimented and conducted an analysis regarding the potential for fabrication of amorphous polymeric microspheres. The researchers evaluated microsphere size, morphology, and texture. Ultimately, they were able to produce ‘near-perfect microspheres.’

“We discovered intricate physical phenomena governing the mechanism of sphere-formation; beside process and performance efficiencies, which in turn render microsphere products more accessible,” stated the researchers. “SPHRINT printing eliminates the use of organic solvents and surfactants; it offers microspheres with reproducible size, shape, and morphology within and between the batches; and the produced microspheres can be easily collected owing to their spherical shape.”

Jetting rate and shear rate were calculated, along with an investigation of melt interaction with the superoleophobic substrate and sphere formation.

In terms of drug encapsulation efficiency, they found that values in connection with SPHRINT were on the highest scale. The authors were encouraged to find ‘stable, consistent, reproducible results.’

“… we believe that SPHRINT may turn microsphere production ubiquitous, allowing for desktop manufacturing of microspheres easily scalable to industrial quantities (with a production rate of 25 Hz, in 1 h, 4.7 g of PCL microspheres may be printed from a single printing head). Finally, SPHRINT may provide a new dimension in reservoir-injectable drug delivery technologies, enabling the employment of multifarious polymers for microsphere production and tuned release profiles,” concluded the researchers.

3D printing has been used in connection with a variety of different drug delivery systems, from experimenting with microreservoirs to hydrophilic matrices, and even spermbots. What do you think of this news? Let us know your thoughts; join the discussion of this and other 3D printing topics at 3DPrintBoard.com.

[Source / Images: ‘SPHRINT – Printing Drug Delivery Microspheres from Polymeric Melts’]

The post 3D Printing Microstructures for New Drug Delivery Systems with SPHRINT appeared first on 3DPrint.com | The Voice of 3D Printing / Additive Manufacturing.

Added Scientific Used Xaar Printhead in Pilot Project for 3D Printing Personalized Pharmaceuticals

Cambridge-based company Xaar may have had its start in developing piezoelectric, drop-on-demand industrial printheads, but transitioned to the 3D printing world back in 2014 when it helped develop the high speed sintering (HSS) FACTUM 3D printer. Xaar is also a leading developer of digital inkjet printing technology, and is currently helping research organization Added Scientific, headquartered in Nottingham, as it works to determine how suitable inkjet printing is in fabricating personalized pharmaceuticals.

Added Scientific, a spinoff company from the University of Nottingham, is using Xaar’s 1201 printhead to bring personalized medicine, with dosages tailored to individual people on an industrial scale, just one step closer to reality.

Craig Sturgess, Research Manager for Added Scientific, said, “Inkjet printing offers the ability to digitally control the printing with its precision placement of tiny droplets a few picolitres in size and the capability to place multiple materials to create complex multi-functional objects in 2D & 3D.

The project was initiated by Added Scientific with its collaborating partners Xaar and global pharmaceutical company AstraZeneca and funded under the UK government’s Industrial Strategy Challenge Fund’s Medicines Manufacturing Challenge, with additional support from Innovate UK. They’re building on research previously conducted at the university regarding the development of excipients: everything but the active pharmaceutical ingredient (API). This pilot project is looking at the long-term suitability and scalability of using inkjet printing to dispense APIs.

“Trial research carried out previously has shown that inkjet offers a real potential for printed medicines. This project was designed to answer questions pharmaceutical companies have around the suitability of inkjet printing in dispensing APIs at a scale that made both manufacturing and economic sense,” Sturgess continued.

The project partners used the Xaar 1201 printhead with one of the university’s formulations to evaluate its impact on the API, in addition to how well it can operate under Good Manufacturing Practice (GMP) conditions. GMP is the de facto standard for manufacturing in the pharmaceutical industry. They also studied if the formulation had an effect on the life of the printhead, and rounded out their experimental trials by evaluating AstraZeneca’s data from conventional tablet manufacturing against inkjet printing process times.

Xaar’s 1201 printhead

“The Xaar 1201 is ideal for a wide range of industrial applications including Advanced Manufacturing due to its ability to print fluids with a range of viscosities, reactivity and conductivity. This pilot project has demonstrated the Xaar 1201’s versatility for pharmaceuticals and how inkjet printing is proving itself to have the potential to drive innovation as well as efficiencies in many areas of 21 st century life,” stated Mike Seal, Business Development Manager, Advanced Manufacturing, at Xaar.

The results from the team’s project showed significant time saved in unit process times from inkjet printing in comparison to conventional manufacturing methods. Production trials consisted of 1,000 dosage forms printed in batches of 100, and no issues or interaction with the API occurred in Xaar’s 1201 printhead; additionally, there was no impact on the life of the printhead itself.

“These are exciting times. Our project has clearly shown that printing personalised medicines – with all their advantages of dose and design freedom – is no longer just a theory, but a scalable and economic reality for pharmaceutical companies and we look forward to extended trials to confirm these findings,” Sturgess concluded.

Added Scientific and its project partners are certainly not the first to investigate the idea of using 3D printing to fabricate personalized medication, and I doubt they will be the last. However, inkjet printing is not typically used to make 3D printed medication, so it will be interesting to see what the team’s next steps will be.

Discuss this story and other 3D printing topics at 3DPrintBoard.com or share your thoughts in the Facebook comments below.

[Images: Xaar]