August 23, 2018

Practical Applications for 3DP Drug Manufacturing: Today and Tomorrow


The emergence of 3DP for Pharma is a significant industry advancement, as it will ultimately revolutionize the way we manufacture drugs in the digital age. Any company that seeks competitive advantage through an offering strategy that includes personalized or precision medicine will find 3DP manufacturing critical to their success. 3DP manufacturing will enable pharmaceutical companies to tailor the dose, release profile, size and shape of a drug to meet the unique or changing medical needs of special populations.

At Aprecia, we visualize our proprietary 3DP manufacturing system, equipment assemblies and processes as a platform from which it is possible to design and produce, at commercial scale, advanced dosage forms and formulations. Such dosage forms and formulations are often beyond the technical limits of conventional solid oral dosage form manufacturing systems. Aprecia continues to refine and evolve our 3DP technology platform to maximize its promise and potential for the pharmaceutical industry. At present, the pharmaceutical industry can benefit from Aprecia’s 3DP for Pharma in the following ways.

What's Possible with 3DP Today

With so many application possibilities, it would be easy to let the imagination run wild and try to do too much too fast. Therfore, to start our innovation journey with 3DP for Pharma, we focused on the development and validation of ZipDose Technology, the world’s first and only FDA-validated, commercial-scale 3DP for pharma. Aprecia adapted powder liquid 3DP technology developed at MIT to innovate ZipDose Technology. The process involves the use of print fluids to bind layers of API-containing powder together into porous structures or dosage forms. The ZipDose formulation platform is ready and immediately available to develop and manufacture advanced fast melt dosage forms that accommodate large drug loads yet disperse very quickly with a sip of liquid. Today, ZipDose technology is opening new possibilities in new therapeutic areas for drug manufacturers and is helping patients who need medicines that are easy to take and caregivers who want medicines that are easy to administer.

Advantages over Conventional Fast Melt

ZipDose technology can address a major limitation of commercially available fast melt manufacturing technologies, which is a “dose ceiling” above which it becomes extremely difficult to achieve rapid disintegration and acceptable “mouth feel” for the patient. While there are many examples of successful low dose (<30mg) products enabled by commercially available fast melt technologies, the advantages of a precise dose and immediate dispersion are needed most when the patient is prescribed a high dose of their medication (>50mg) or the regimen is challenging in terms of adherence.  ZipDose formulations are often the only way those advantages can be realized together.

Advantages over Liquid Technologies

Unlike liquids and suspensions, ZipDose formulations require no measuring, are precise, spill proof, and easily transported, utilizing sophisticated taste masking techniques such as coating, encapsulation, complexation and particle engineering to improve the taste and enhance the experience.

Accommodating other technologies

ZipDose Technology does not use any direct compression forces during the 3DP manufacturing process and is not subject to the same size limitations as a conventional tablet or capsule due to rapid oral dispersion. Therefore, it is possible to coat or encapsulate drug particles for taste masking purposes as described above or to alter the release characteristics of the product. This means a product that combines the advantages of rapid dispersion along with a modified release profile is feasible.

Accommodating Multiple Active Pharmaceutical Ingredients

Less limitation on tablet size also means more room to design formulations that contain multiple APIs within the powder blend. Additionally, it is possible to print certain APIs if desirable. This means a fixed-dosed combination product containing multiple APIs with rapid disperse functionality is feasible.

More than Rapid Oral Dispersion

With ZipDose technology, it is possible to control tablet harness and disintegration time by altering the print image and the amount of liquid deposited during a build cycle. Therefore, the platform may also offer a means by which to design formulations with enhanced buccal or sublingual absorption or site-specific delivery within the GI tract.

Applications in Early Phase Drug Development

It is possible to expedite early-phase drug development (such as preclinical studies and first-in-human trials) by using 3DP to produce on demand formulations with excellent dose flexibility quickly and at low cost. 3DP could also support formulation development because it has the capability to produce rapid product iterations for testing, such as excipient compatibility and drug release.

Imagining Future Applications Enabled by 3DP

As we evolve our 3DP manufacturing systems, equipment assemblies and processes, it may be possible to develop additional applications for the technology.

  • As we build 3DP dosage forms layer-by-layer, it may be possible to incorporate anti-counterfeiting properties. This application of the technology involves the printing of a company mark (e.g., name, brand, etc.) within the inner layers of the dosage form.
  • The precise control over droplet size and reproducibility offered by 3DP manufacturing may enable the printing of drug-loaded fluids onto an excipient powder bed to form (complex) immediate, extended, and multi-release dosage forms. This approach would enable the formulator to vary the microarchitecture of the dosage form and print drug concentration gradients by controlling droplet size and placement within the microarchitecture.
  • The precise control and reproducibility of droplet size offered by 3DP manufacturing may lead to safer preparation of drug delivery systems for highly toxic and potent drugs. Because drug deposited via fluid can provide highly accurate dosing it may be safer than handling powders.
  • 3DP technology may also benefit implantable drug delivery systems by offering effective strategies to overcome limitations such as batch-to-batch drug variability and excipient blend during implant preparation and inconsistent internal architecture of resultant implants. 3DP technologies can produce implants that have precisely defined, micro- and macro architectures that enable complex drug release. 3DP may also offer advantages in optimizing the concentration of drug needed in implant preparation that could be important for improving drug efficacy and minimizing toxicity and side effects.