Understanding Direct Powder Extrusion for Fabrication of 3D Printed Personalised Medicines: A Case Study for Nifedipine Minitablets

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.

Direct cyclodextrin-based powder extrusion 3D printing for one-step production of the BCS class II model drug niclosamide

“…The printed tablets had an average diameter ranging from 11.63 mm to 12.15 mm, and the average height ranged from 3.49 mm to 3.74 mm. This accuracy in the printing of the tablets was confirmed by data reported in the literature obtained with the same printing method [ 41 , 42 ]. The average mass was described as ranging from 414.00 to 506.80 mg, this variation could be due to the different composition of the individual blends, which gives the powders different flow properties in the extruder.…”

Tailoring Rational Manufacturing of Extemporaneous Compounding Oral Dosage Formulations with a Low Dose of Minoxidil

“…The impacts of the four different variables described above were investigated on five responses: the percentage of minoxidil content (compared to the theoretical 100%), mass content, dosage uniformity of minoxidil and riboflavin (%), and mass variation ( Table 1 ). Polynomial regression models were calculated targeting a minimization of the minoxidil content variability when preparing extemporaneous compounding minoxidil oral formulations to reduce undesirable adverse effects [ 7 ].…”

3D Printing Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals

“…However, the main challenge to overcome when using FDM is the manufacturing of high-quality filaments and working with thermolabile APIs. The solution for the first issue is to use direct power extrusion (DPE) or semisolid extrusion (SSE) instead of FDM, and for the letter challenge, PAM techniques can be used instead [ 40 , 41 , 42 , 43 , 44 , 45 ].…”