Solvent-free Temperature-Facilitated Direct Extrusion 3D Printing for Pharmaceuticals

Kuzminska, Magda, Pereira, Beatriz, Habashy, Rober, Peak, Matthew, Isreb, Mohammad, Gough, Tim D, Isreb, Abdullah orcid iconORCID: 0000-0001-9939-6161 and Alhnan, Mohamed A (2021) Solvent-free Temperature-Facilitated Direct Extrusion 3D Printing for Pharmaceuticals. International Journal of Pharmaceutics . ISSN 1873-3476

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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 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. [Abstract copyright: Copyright © 2021. Published by Elsevier B.V.]

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