King's College London

Research portal

Solvent-free temperature-facilitated direct extrusion 3D printing for pharmaceuticals

Research output: Contribution to journalArticlepeer-review

Magdalena Kuźmińska, Beatriz C. Pereira, Rober Habashy, Matthew Peak, Mohammad Isreb, Tim D. Gough, Abdullah Isreb, Mohamed A. Alhnan

Original languageEnglish
Article number120305
JournalINTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume598
DOIs
Published1 Apr 2021

Bibliographical note

Publisher Copyright: © 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

In an era moving towards digital health, 3D printing has successfully proven its applicability in providing personalised medicine through a technology-based approach. Among the different 3D printing techniques, direct extrusion 3D printing has been demonstrated as a promising approach for on demand manufacturing of solid dosage forms. However, it usually requires the use of elevated temperatures and/or the incorporation of an evaporable solvent (usually water). This can implicate the addition of a drying step, which may compromise the integrity of moisture- or temperature-sensitive drugs, and open the door for additional quality control challenges. Here, we demonstrate a new approach that simplifies direct extrusion 3D printing process with the elimination of the post-printing drying step, by merely adding a fatty glyceride, glyceryl monostearate (GMS), to a model drug (theophylline) and permeable water insoluble methacrylate polymers (Eudragit RL and RS). Indeed, rheological studies indicated that the addition of a combination of a plasticiser, (triethyl citrate), and GMS to theophylline: methacrylate polymer blends significantly reduced the extensional viscosity (to <2.5 kPa·Sec) at 90 °C. Interestingly, GMS demonstrated a dual temperature-dependant behaviour by acting both as a plasticiser and a lubricant at printing temperature (90–110 °C), while aiding solidification at room temperature. X-ray powder diffraction indicated incomplete miscibility of GMS within the polymeric matrix at room temperature with the presence of a subtle diffraction peak, at 2(Θ) = 20°. The 3D printed tablets showed acceptable compendial weight and content uniformity as well as sufficient mechanical resistance. In vitro theophylline release from 3D printed tablets was dependant on Eudragit RL:RS ratio. All in all, this work contributes to the efforts of developing a simplified, facile and low-cost 3D printing for small batch manufacturing of bespoke tablets that circumvents the use of high temperature and post-manufacturing drying step.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454