Effect of pH, Ionic Strength and Agitation Rate on Dissolution Behaviour of 3D-Printed Tablets, Tablets Prepared from Ground Hot-Melt Extruded Filaments and Physical Mixtures

Nour Nashed; Stephanie Chan; Matthew Lam; Taravat Ghafourian; Ali Nokhodchi

doi:10.3390/biomedicines11020375

Effect of pH, Ionic Strength and Agitation Rate on Dissolution Behaviour of 3D-Printed Tablets, Tablets Prepared from Ground Hot-Melt Extruded Filaments and Physical Mixtures

Biomedicines. 2023 Jan 27;11(2):375. doi: 10.3390/biomedicines11020375.

Authors

Nour Nashed¹, Stephanie Chan¹, Matthew Lam², Taravat Ghafourian³, Ali Nokhodchi^{1

4}

Affiliations

¹ Pharmaceutics Research Laboratory, Arundel Building, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK.
² Department of Chemical and Pharmaceutical Sciences, School of Human Sciences, London Metropolitan University, 166-220 Holloway Road, London N7 8DB, UK.
³ Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, FL 33328, USA.
⁴ Lupin Inhalation Research Center, 4006 NW 124th Ave., Coral Springs, FL 33065, USA.

Abstract

With the current focus on 3D-printing technologies, it is essential to understand the processes involved in such printing methods and approaches to minimize the variability in dissolution behaviour to achieve better quality control outcomes. For this purpose, two formulations of theophylline tablets were prepared using hydroxypropyl cellulose (HPC) and ethyl cellulose (EC). Among the two types of tablets, three different methods (physical mixture (PM), hot-melt extrusion (HME) and 3D-printing fused deposition modelling (FDM)) were applied and their dissolution behaviours were studied under various conditions using a biodissolution tester. This was carried out at pH values of 1.2, 2.2, 5.8, 6.8, 7.2 and 7.5, mimicking the medium in the gastrointestinal tract. Dissolution tests under two dipping rates (10 dpm and 20 dpm) and two ionic strengths (0.2 M and 0.4 M) were conducted to mimic fed and fasting conditions. The dissolution efficiency (DE%), release rate, similarity factor (f₂) and difference factor (f₁) were calculated. When comparing the DE%, the formulation containing EC showed less sensitivity to changes in the dipping rate and ionic strength compared to the HPC formulation. As for the manufacturing method, 3D-printing FDM could improve the robustness of the dissolution behaviour of both formulations to dipping rate changes. However, for ionic strength changes, the effect of the manufacturing method was dependent on the formulation composition. For example, the 3D-printed tablets of the HPC formulation were more sensitive to changes in ionic strength compared to the EC-containing formulation. The release mechanism also changed after the thermal process, where n values in the Korsmeyer-Peppas model were much higher in the printing and HME methods compared to the PM. Based on the formulation composition, the 3D-printing method could be a good candidate method for tablets with a robust dissolution behaviour in the GI tract. Compared to HPC polymers, using hydrophobic EC polymers in printable formulations can result in a more robust dissolution behaviour in fed and fasting states.

Keywords: 3D printing; agitation rate; biodissolution; hot-melt extrusion; ionic strength; physical mixture.

Grants and funding

This research received no external funding.