3D printed spherical mini-tablets : geometry versus composition effects in controlling dissolution from personalised solid dosage forms

Ayyoubi, Sejad and Cerda, Jose R. and Fernández-García, Raquel and Knief, Peter and Lalatsa, Aikaterini and Healy, Anne Marie and Serrano, Dolores R. (2021) 3D printed spherical mini-tablets : geometry versus composition effects in controlling dissolution from personalised solid dosage forms. International Journal of Pharmaceutics, 597. 120336. ISSN 0378-5173 (https://doi.org/10.1016/j.ijpharm.2021.120336)

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Abstract

Oral dosage forms are by far the most common prescription and over-the-counter pharmaceutical dosage forms used worldwide. However, many patients suffer from adverse effects caused by their use of "one-size fits all" mass produced commercially available solid dosage forms, whereby they do not receive dedicated medication or dosage adjusted to their specific needs. The development of 3D printing paves the way for personalised medicine. This work focuses on personalised therapies for hypertensive patients using nifedipine as the model drug. 3D printed full solid and channelled spherical mini-tablets with enhanced surface area (1.6-fold higher) were printed using modified PVA commercial filaments loaded by passive diffusion (PD), and Kollidon VA64 (KVA) and ethylcellulose (EC) based filaments prepared by hot-melt extrusion (HME). Drug loading ranged from 3.7% to 60% based on the employed technique, with a 13-fold higher drug loading achieved with the HME compared to PD. Composition was found to have a more significant impact on drug dissolution than geometry and surface area. Both KVA and EC-based formulations exhibited a biphasic zero-order drug-release profile. Physicochemical characterization revealed that nifedipine was in the amorphous form in the KVA-based end-products which led to a greater dissolution control over a 24 h period compared to the EC-based formulations that exhibited low levels of crystallinity by PXRD. The proposed 3D printed spherical mini-tablets provide a versatile technology for personalised solid dosage forms with high drug loading and dissolution control, easily adaptable to patient and disease needs.

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