Personalizing oral delivery of nanoformed piroxicam by semi-solid extrusion 3D printing

Semi-solid extrusion (SSE) 3D printing enables flexible designs and dose sizes to be printed on demand and is a suitable tool for fabricating personalized dosage forms. Controlled Expansion of Supercritical Solution (CESS®) is a particle size reduction technology, and it produces particles of a pure active pharmaceutical ingredient (API) in a dry state, suspendable in the printing ink. In the current study, as a model API of poorly water-soluble drug, nanoformed piroxicam (nanoPRX) prepared by CESS® was accommodated in hydroxypropyl methylcellulose- or hydroxypropyl cellulose-based ink formulations to warrant the printability in SSE 3D printing. Importantly, care must be taken when developing nanoPRX formulations to avoid changes in their polymorphic form or particle size. Printing inks suitable for SSE 3D printing that successfully stabilized the nanoPRX were developed. The inks were printed into films with escalating doses with exceptional accuracy. The original polymorphic form of nanoPRX in the prepared dosage forms was not affected by the manufacturing process. In addition, the conducted stability study showed that the nanoPRX in the prepared dosage form remained stable for at least three months from printing. Overall, the study rationalizes that with nanoparticle-based printing inks, superior dose control for the production of personalized dosage forms of poorly water-soluble drugs at the point-of-care can be achieved.

2. Materials

NanoPRX, provided by Nanoform Finland Plc. (Helsinki, Finland), was used as received. Three different polymers were studied for stabilizing the nanoPRX, hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC), and a polyvinyl alcohol-polyethylene glycol graft copolymer (PEG-PVA). HPC (Klucel EXF) was kindly provided by Ashland (Schaffhausen, Switzerland) and PEG-PVA (Kollicoat Protect) by BASF SE (Ludwigshafen, Germany). Several HPMC grades from different producers with various methoxy and hydroxypropyl substitutions were investigated (specific details in (Table A.1). Tylopur (603, 605, and 606), Methocel (E5 Premium LV and K3 LV), and Benecel (K100 LV, K100 M, and K15 M) were kindly donated by SE Tylose GmbH & Co.KG (Wiesbaden, Germany), Dow Chemical Company (Bomlitz, Germany), and Ashland (Schaffhausen, Switzerland), respectively. Tween 80 was purchased from Sigma Aldrich (Steinheim, Germany). To prepare the aqueous polymer dispersions, three different film-forming polymers were investigated; HPMC (Tylopur® 605), HPC (Klucel™ EXF), and PEG-PVA (Kollicoat® Protect). Glycerol, purchased from Sigma Aldrich (St. Louis, MO, USA), was used as a plasticizer in the aqueous polymer dispersions. Purified water (MQ) (Milli-Q® water) and ethanol (EtOH) (Etax A 94 w-%, Altia Oyj, Rajamäki, Finland) were used as solvents. All water in this study was purified by a Millipore SA-67120 system from Millipore (Molsheim, France). To create a cross-section for SEM imaging, printed objects were frozen with liquid nitrogen (Oy Linde Gas Ab, Finland). Sodium phosphate monobasic (Sigma-Aldrich, Germany), sodium chloride (VWR International Oy, Finland), and sodium hydroxide (Merck, Germany) were used to prepare the phosphate media.

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Rathna Mathiyalagan, Erica Sjöholm, Sajana Manandhar, Satu Lakio, Jessica M. Rosenholm, Martti Kaasalainen, Xiaoju Wang, Niklas Sandler, Personalizing oral delivery of nanoformed piroxicam by semi-solid extrusion 3D printing, European Journal of Pharmaceutical Sciences, Volume 188, 2023, 106497, ISSN 0928-0987,
https://doi.org/10.1016/j.ejps.2023.106497.