ABSTRACT
3D printing technologies enable medicine customization adapted to patients' needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines. 3D-printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained-release 3D-printed implants, stents, and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines, such as wound dressing, microneedles, and medicated contact lenses, have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing technique most suitable for each application and the type of pharmaceutical ink that should be developed that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing ("nanoprinting") brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice.
ABSTRACT
Fuse deposition modelling (FDM) has emerged as a novel technology for manufacturing 3D printed medicines. However, it is a two-step process requiring the fabrication of filaments using a hot melt extruder with suitable properties prior to printing taking place, which can be a rate-limiting step in its application into clinical practice. Direct powder extrusion can overcome the difficulties encountered with fabrication of pharmaceutical-quality filaments for FDM, allowing the manufacturing, in a single step, of 3D printed solid dosage forms. In this study, we demonstrate the manufacturing of small-weight (<100 mg) solid dosage forms with high drug loading (25%) that can be easily undertaken by healthcare professionals to treat hypertension. 3D printed nifedipine minitablets containing 20 mg were manufactured by direct powder extrusion combining 15% polyethylene glycol 4000 Da, 40% hydroxypropyl cellulose, 19% hydroxy propyl methyl cellulose acetate succinate, and 1% magnesium stearate. The fabricated 3D printed minitablets of small overall weight did not disintegrate during dissolution and allowed for controlled drug release over 24 h, based on erosion. This release profile of the printed minitablets is more suitable for hypertensive patients than immediate-release tablets that can lead to a marked burst effect, triggering hypotension. The small size of the minitablet allows it to fit inside of a 0-size capsule and be combined with other minitablets, of other API, for the treatment of complex diseases requiring polypharmacy within a single dosage form.
