Digital Compounding in Pharmacies: A Pilot Stability Study †

The manufacture of medicines on demand for a particular patient, at the point of care, may be achieved via 3D printing, improving therapeutic outcomes, medication adherence and patient safety. Tablets are often printed using a combination of hot-melt extrusion and fused deposition modelling. In this work, paracetamol-loaded hydroxypropylcellulose filaments were produced; their extrudability and printability were aided by a plasticizer and a lubricant. For printability, 11% humidity was the ideal storage condition for filaments up to 6 months. The tablets produced complied with the uniformity of mass and content requirements, and showed delayed drug release; these characteristics were maintained after in-use stability testing for 30 days.

1.Introduction

The patient-centric design and manufacture of medicines may be achieved via 3D printing (3DP), an emergent technology that allows the digital customization of the dose and/or the design of the dosage form to tailor drug release [1]. Likewise, the on-demand manufacture of dosage units containing several drugs, according to a distinct dose and prescription regimen, simplifies life and increases compliance and the safety of polymedicated individuals.

Due to its simplicity, cost-effectiveness and versatility, fused deposition modelling (FDM) is one of the most popular 3DP techniques, comprising the successive layering of a molten drug-loaded thermoplastic polymer. FDM has been extensively used in the preparation of simple or complex dosage forms [2], with a variety of doses, shapes and release kinetics. However, besides being inadequate for heat-sensitive drugs [1], printers have to be fed with filaments, which are commercially unavailable. As such, these have to be produced beforehand using hot-melt extrusion (HME), increasing the duration and complexity of the manufacture. Depending on the formulation and processing parameters used, the integration of HME and FDM may not be straightforward [1], and may require evaluation and tuning. For compounding, it is also critical to expedite the process.

Since FDM printers are economical, compact and easy to operate, the decentralization of production from large pharmaceutical industries to community pharmacies and local hospitals is possible [3], being viable even in remote locations and when supply chains are disrupted. In addition to the potential of digital compounding to meet individual medical/clinical needs, the technology will also add value to the role of the pharmacist.

The production of medicines on demand at the dispensing site would benefit from stocking filaments (pre-produced in-house or industrially from a range of polymeric matrices and different drugs/drug loads for dose flexibility) that would be fed into the printer when and as required, according to the needs of a particular patient. The stability of filaments is a major concern, particularly of those produced using cellulosic matrices, which are hygroscopic and lose printability due to the plasticizing effect of water [2].

Therefore, the aim of this work was to establish formulation and processing parameters, as well as storage conditions for filaments, to maximize shelf-life while maintaining printability for the production of tablets, tailored to a specific patient, at the point of care. The stability of filaments was evaluated over time under different moisture conditions; the in-use stability of the 3D-printed tablets was also evaluated up to 30 days in defined relative humidity (RH) environmental settings.

2. Materials and Methods

Paracetamol (PCT; AcoFarma, Madrid, Spain) was used as a model drug, and hydroxypropylcellulose (HPC; Klucel LF^®, Ashland, Wilmington, DE, USA), Soluplus^® (SLP; BASF, Ludwigshafen, Germany) and magnesium stearate (MgS; Roic Farma, Barcelona, Spain) were used as excipients. Lithium chloride (11% RH), magnesium nitrate (53% RH), sodium chloride (75% RH), potassium nitrate (93% RH), silica gel (below 40% RH) and HPLC-grade methanol were supplied by Sigma Aldrich (Darmstadt, Germany).

Six different drug-loaded filaments (F1–F6; Table 1 for composition) were produced by HME using a single-screw extruder (Noztek Pro, Noztek, Shoreham, UK; nozzle die diameter of 1.5 mm, screw speed of 20 rpm, extruding temperature of 100 ± 2 °C and 65 ± 2 °C).

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Fernandes, A.I.; Pereira, G.G.; Pinto, J.F. Digital Compounding in Pharmacies: A Pilot Stability Study. Med. Sci. Forum 2023, 22, 9.
https://doi.org/10.3390/msf2023022009

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