3D Printed Pellets (Miniprintlets): A Novel, Multi-Drug, Controlled Release Platform Technology

Winner of the Pharmaceutics 2021 Best Paper Awards

Selective laser sintering (SLS) is a single-step three-dimensional printing (3DP) process that can be leveraged to engineer a wide array of drug delivery systems. The aim of this work was to utilise SLS 3DP, for the first time, to produce small oral dosage forms with modified release properties. As such, paracetamol-loaded 3D printed multiparticulates, termed miniprintlets, were fabricated in 1 mm and 2 mm diameters. Despite their large surface area compared with a conventional monolithic tablet, the ethyl cellulose-based miniprintlets exhibited prolonged drug release patterns.

The possibility of producing miniprintlets combining two drugs, namely paracetamol and ibuprofen, was also investigated. By varying the polymer, the dual miniprintlets were programmed to achieve customised drug release patterns, whereby one drug was released immediately from a Kollicoat Instant Release matrix, whilst the effect of the second drug was sustained over an extended time span using ethyl cellulose. Herein, this work has highlighted the versatility of SLS 3DP to fabricate small and intricate formulations containing multiple active pharmaceutical ingredients with distinct release properties.

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Article information: Awad, A.; Fina, F.; Trenfield, S.J.; Patel, P.; Goyanes, A.; Gaisford, S.; Basit, A.W. 3D Printed Pellets (Miniprintlets): A Novel, Multi-Drug, Controlled Release Platform Technology. Pharmaceutics 2019, 11, 148. https://doi.org/10.3390/pharmaceutics11040148

Materials and Methods
Paracetamol USP grade (MW 151.16 g/mol, solubility in water at 37 °C: 21.80 g/L) and ibuprofen (sodium salt; MW 228.26 g/mol, solubility in water: 100 g/L) (both from Sigma-Aldrich, Poole, UK) were used as model drugs. Ethyl cellulose N7 was obtained from Ashland, Schaffhausen, Switzerland and Kollicoat Instant Release (IR) was obtained from BASF, Ludwigshafen, Germany. Candurin Gold Sheen was purchased from Merck, Darmstadt, Germany. The salts for preparing the buffer dissolution media were purchased from VWR International Ltd., Leicestershire, UK.

Conclusions
In this work, we demonstrated that miniprintlets prepared using SLS 3DP offer a novel drug delivery approach with high flexibility and control over the drug content and release properties. Fine-tuning of the therapeutic effect can be achieved by modulating parameters such as the dimensions and matrix composition, which in turn can be leveraged to produce multi-drug systems. To our knowledge, this study is the first to demonstrate the possibility of combining two rate-controlling systems in such small and intricate pharmaceutical dosage forms, enabling the individual programming of each drug. As such, this emphasises the value of this technology, making it favourable over other commercial fabrication systems for the production of pharmaceuticals.