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

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.

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Materials: NFD was purchased from Industria Chimica Italiana (>95%, Bergamo, Italy). Hypromellose acetate succinate (HPMCAS) (AQOAT^® LG grade) was a gift from Shin-Etsu (Tokyo, Japan). PEG 4000 and magnesium stearate were purchased from Sigma-Aldrich (Madrid, Spain). Kollidon VA 64 (KVA64) was a gift from BASF (Ludwigshafen, Germany). Klucel hydroxypropyl cellulose (HPC, 95 kDa) LF grade was kindly donated by Ashland (Madrid, Spain). Solvents were HPLC grade and were purchased from Proquinorte (Madrid, Spain). Any other reagents were used without further purification and were of analytical grade.

Article information: Sánchez-Guirales, S.A.; Jurado, N.; Kara, A.; Lalatsa, A.; Serrano, D.R. Understanding Direct Powder Extrusion for Fabrication of 3D Printed Personalised Medicines: A Case Study for Nifedipine Minitablets. Pharmaceutics 2021, 13, 1583. https://doi.org/10.3390/pharmaceutics13101583