Solvent-free temperature-facilitated direct extrusion 3D printing for pharmaceuticals

Kuźmińska, Magdalena; Pereira, Beatriz C.; Habashy, Rober; Peak, Matthew; Isreb, Mohammad; Gough, Tim; Isreb, Abdullah; Alhnan, Mohamed Albed

doi:10.1016/j.ijpharm.2021.120305

Cited by 32 publications

(30 citation statements)

References 46 publications

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“…In addition, a very recent study describes the development of modified release theophylline tablets with direct extrusion 3D printing, eliminating the drying step after printing [ 93 ]. This was achieved by adding a fatty glyceride, glyceryl monostearate (GMS), and water-insoluble methacrylate polymers (Eudragit ® RL and RS).…”

Section: Resultsmentioning

confidence: 99%

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3D-Printed Oral Dosage Forms: Mechanical Properties, Computational Approaches and Applications

et al. 2021

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The aim of this review is to present the factors influencing the mechanical properties of 3D-printed oral dosage forms. It also explores how it is possible to use specific excipients and printing parameters to maintain the structural integrity of printed drug products while meeting the needs of patients. Three-dimensional (3D) printing is an emerging manufacturing technology that is gaining acceptance in the pharmaceutical industry to overcome traditional mass production and move toward personalized pharmacotherapy. After continuous research over the last thirty years, 3D printing now offers numerous opportunities to personalize oral dosage forms in terms of size, shape, release profile, or dose modification. However, there is still a long way to go before 3D printing is integrated into clinical practice. 3D printing techniques follow a different process than traditional oral dosage from manufacturing methods. Currently, there are no specific guidelines for the hardness and friability of 3D printed solid oral dosage forms. Therefore, new regulatory frameworks for 3D-printed oral dosage forms should be established to ensure that they meet all appropriate quality standards. The evaluation of mechanical properties of solid dosage forms is an integral part of quality control, as tablets must withstand mechanical stresses during manufacturing processes, transportation, and drug distribution as well as rough handling by the end user. Until now, this has been achieved through extensive pre- and post-processing testing, which is often time-consuming. However, computational methods combined with 3D printing technology can open up a new avenue for the design and construction of 3D tablets, enabling the fabrication of structures with complex microstructures and desired mechanical properties. In this context, the emerging role of computational methods and artificial intelligence techniques is highlighted.

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Section: Resultsmentioning

confidence: 99%

“…This can be explained by the lower number of quaternary ammonium groups and consequently the lower hydrophilicity of Eudragit ® RS compared to Eudragit ® RL. Thus, by choosing the appropriate methacrylate polymer ratio, it is possible to tailor the drug release profile [ 93 ].…”

Section: Resultsmentioning

confidence: 99%

3D-Printed Oral Dosage Forms: Mechanical Properties, Computational Approaches and Applications

et al. 2021

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“…Finally, the blends (approximately 10 g) were filled in a 12 mm diameter metal syringe (Hyrel 3D, Atlanta, GA, USA) to produce the tablet ( Figure 7 ). The work revealed a simplified, facile, and low-cost 3D printing for small-batch manufacturing of bespoke tablets that circumvents the use of high temperature and post-manufacturing drying [ 58 ].…”

Section: Resultsmentioning

confidence: 99%

“…( B ) Top and ( C ) side photographs of 3D-printed tablets based on Eudragit RL: RS: 100:0, 75:25, 50:50, 25:75, and 0:100. Figures reproduced with permission from [ 58 ]. Copyright Elsevier, 2021.…”

Section: Figurementioning

confidence: 99%

3D Printing of Thermo-Sensitive Drugs

et al. 2021

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Three-dimensional (3D) printing is among the rapidly evolving technologies with applications in many sectors. The pharmaceutical industry is no exception, and the approval of the first 3D-printed tablet (Spiratam®) marked a revolution in the field. Several studies reported the fabrication of different dosage forms using a range of 3D printing techniques. Thermosensitive drugs compose a considerable segment of available medications in the market requiring strict temperature control during processing to ensure their efficacy and safety. Heating involved in some of the 3D printing technologies raises concerns regarding the feasibility of the techniques for printing thermolabile drugs. Studies reported that semi-solid extrusion (SSE) is the commonly used printing technique to fabricate thermosensitive drugs. Digital light processing (DLP), binder jetting (BJ), and stereolithography (SLA) can also be used for the fabrication of thermosensitive drugs as they do not involve heating elements. Nonetheless, degradation of some drugs by light source used in the techniques was reported. Interestingly, fused deposition modelling (FDM) coupled with filling techniques offered protection against thermal degradation. Concepts such as selection of low melting point polymers, adjustment of printing parameters, and coupling of more than one printing technique were exploited in printing thermosensitive drugs. This systematic review presents challenges, 3DP procedures, and future directions of 3D printing of thermo-sensitive formulations.

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“…The benefits of this type of printing are the low printing temperature, allowing handling of even thermolabile drugs, and the use of disposable syringes, which can guarantee a high quality and purity of the end product [ 18 ]. In this type of printing, the viscosity of the printing ink is crucial for the end product properties, while the rheological properties reflect the printing performance [ 19 ]. For example, polymer concentration is related to the viscosity of the printing ink: when the viscosity of the feeding liquid/suspension is lowered, also the printing pressure is lowered [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

3D Printing of Drug Nanocrystals for Film Formulations

Germini

Peltonen

2021

Molecules

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The aim of the study was to prepare indomethacin nanocrystal-loaded, 3D-printed, fast-dissolving oral polymeric film formulations. Nanocrystals were produced by the wet pearl milling technique, and 3D printing was performed by the semi-solid extrusion method. Hydroxypropyl methyl cellulose (HPMC) was the film-forming polymer, and glycerol the plasticizer. In-depth physicochemical characterization was made, including solid-state determination, particle size and size deviation analysis, film appearance evaluation, determination of weight variation, thickness, folding endurance, drug content uniformity, and disintegration time, and drug release testing. In drug nanocrystal studies, three different stabilizers were tested. Poloxamer F68 produced the smallest and most homogeneous particles, with particle size values of 230 nm and PI values below 0.20, and was selected as a stabilizer for the drug-loaded film studies. In printing studies, the polymer concentration was first optimized with drug-free formulations. The best mechanical film properties were achieved for the films with HPMC concentrations of 2.85% (w/w) and 3.5% (w/w), and these two HPMC levels were selected for further drug-loaded film studies. Besides, in the drug-loaded film printing studies, three different drug levels were tested. With the optimum concentration, films were flexible and homogeneous, disintegrated in 1 to 2.5 min, and released the drug in 2–3 min. Drug nanocrystals remained in the nano size range in the polymer films, particle sizes being in all film formulations from 300 to 500 nm. When the 3D-printed polymer films were compared to traditional film-casted polymer films, the physicochemical behavior and pharmaceutical performance of the films were very similar. As a conclusion, 3D printing of drug nanocrystals in oral polymeric film formulations is a very promising option for the production of immediate-release improved- solubility formulations.

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Solvent-free temperature-facilitated direct extrusion 3D printing for pharmaceuticals

Cited by 32 publications

References 46 publications

3D-Printed Oral Dosage Forms: Mechanical Properties, Computational Approaches and Applications

3D-Printed Oral Dosage Forms: Mechanical Properties, Computational Approaches and Applications

3D Printing of Thermo-Sensitive Drugs

3D Printing of Drug Nanocrystals for Film Formulations

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