Direct Powder Extrusion of Paracetamol Loaded Mixtures for 3D Printed Pharmaceutics for Personalized Medicine via Low Temperature Thermal Processing

Abstract

Three-dimensional printed drug development is nowadays an active area in the pharmaceutical industry, where the search for an appropriate edible carrier that permits the thermal processing of the mixture at temperature levels that are safe for the drug is an important field of study. Here, potato starch and hydroxypropyl cellulose based mixtures loaded with paracetamol up to 50% in weight were processed by hot melt extrusion at 85 °C to test their suitability to be thermally processed. The extruded mixtures were tested by liquid chromatography to analyze their release curves and were thermally characterized. The drug recovery was observed to be highly dependent on the initial moisture level of the mixture, the samples being prepared with an addition of water at a ratio of 3% in weight proportional to the starch amount, highly soluble and easy to extrude. The release curves showed a slow and steady drug liberation compared to a commercially available paracetamol tablet, reaching the 100% of recovery at 60 min. The samples aged for 6 weeks showed slower drug release curves compared to fresh samples, this effect being attributable to the loss of moisture. The paracetamol loaded mixture in powder form was used to print pills with different sizes and geometries in a fused deposition modelling three-dimensional printer modified with a commercially available powder extrusion head, showing the potential of this formulation for use in personalized medicine.

Direct cyclodextrin-based powder extrusion 3D printing for one-step production of the BCS class II model drug niclosamide

“…The printed tablets had an average diameter ranging from 11.63 mm to 12.15 mm, and the average height ranged from 3.49 mm to 3.74 mm. This accuracy in the printing of the tablets was confirmed by data reported in the literature obtained with the same printing method [ 41 , 42 ]. The average mass was described as ranging from 414.00 to 506.80 mg, this variation could be due to the different composition of the individual blends, which gives the powders different flow properties in the extruder.…”

3D Printing of Thermo-Sensitive Drugs

“…First, a filament containing Kollidon VA 64, PEG 1500, mannitol, ramipril, and magnesium carbonate was extruded using a single-screw extruder (Noztek Profilament extruder, NozteK, Shoreham-by-Sea, UK) at 70 °C, and subsequently, a tablet containing ramipril was fabricated [ 78 ]. Paracetamol tablets were also successfully produced at a moderate printing temperature of 90 °C using a mixture of potato starch and hydroxypropyl cellulose by employing an FDM printer [ 79 ]. Katsiotis et al demonstrated an interesting concept of increasing thermal stability of drugs using mesoporous magnesium carbonate, which may be useful for protecting thermosensitive drugs against heating applied in FDM [ 80 ].…”

3D Printing Technologies in Personalized Medicine, Nanomedicines, and Biopharmaceuticals

“…However, the main challenge to overcome when using FDM is the manufacturing of high-quality filaments and working with thermolabile APIs. The solution for the first issue is to use direct power extrusion (DPE) or semisolid extrusion (SSE) instead of FDM, and for the letter challenge, PAM techniques can be used instead [ 40 , 41 , 42 , 43 , 44 , 45 ].…”

“…Additionally, poor resolution can be obtained if the powder mixture is not heated evenly. Several examples of personalized medicines, such as paediatric formulations, have been demonstrated using this technique [ 41 , 42 , 43 , 44 ].…”