3D printing (3DP) is forecast to be a highly revolutionary technology within the pharmaceutical sector. In particular, the main benefits of 3DP lie in the production of small batches of medicines, ...each with tailored dosages, shapes, sizes and release characteristics. The manufacture of medicines in this way may finally lead to the concept of personalised medicines becoming a reality. In the shorter term, 3DP could be extended throughout the drug development process, ranging from preclinical development and clinical trials, through to frontline medical care. In this review, we provide a timely perspective on the motivations and potential applications of 3DP pharmaceuticals, as well as a practical viewpoint on how 3DP could be integrated across the pharmaceutical space.
3DP enables the precise deposition of drug and excipients, potentially causing a paradigm shift in medicine design, manufacture and use.
Early-phase drug development (such as preclinical studies and first-in-human trials) could be expedited by using 3DP to rapidly produce formulations with excellent dose flexibility at low cost, on demand.
3DP could support formulation development because it has the capability to produce rapid product iterations for testing, such as excipient compatibility and drug release.
3DP could accelerate the field of personalised medicine by moving treatment away from a ‘one size fits all approach’ towards personalisation.
Display omitted
Three-dimensional (3D) printing is a revolutionary technology that is disrupting pharmaceutical development by enabling the production of personalised printlets (3D printed drug ...products) on demand. By creating small batches of dose flexible medicines, this versatile technology offers significant advantages for clinical practice and drug development, namely the ability to personalise medicines to individual patient needs, as well as expedite drug development timelines within preclinical studies through to first-in-human (FIH) and Phase I/II clinical trials. Despite the widely demonstrated benefits of 3D printing pharmaceuticals, the clinical potential of the technology is yet to be realised. In this timely review, we provide an overview of the latest cutting-edge investigations in 3D printing pharmaceuticals in the pre-clinical and clinical arena and offer a forward-looking approach towards strategies to further aid the translation of 3D printing into the clinic.
Display omitted
Three-dimensional printing (3DP) is a highly disruptive technology with the potential to change the way pharmaceuticals are designed, prescribed and produced. Owing to its low cost, ...diversity, portability and simplicity, fused deposition modeling (FDM) is well suited to a multitude of pharmaceutical applications in digital health. Favourably, through the combination of digital and genomic technologies, FDM enables the remote fabrication of drug delivery systems from 3D models having unique shapes, sizes and dosages, enabling greater control over the release characteristics and hence bioavailability of medications. In turn, this system could accelerate the digital healthcare revolution, enabling medicines to be tailored to the individual needs of each patient on demand. To date, a variety of FDM 3D printed medical products (e.g. implants) have been commercialised for clinical use. However, within pharmaceuticals, certain regulatory hurdles still remain. This article reviews the current state-of-the-art in FDM technology for medical and pharmaceutical research, including its use for personalised treatments and interconnection within digital health networks. The outstanding challenges are also discussed, with a focus on the future developments that are required to facilitate its integration within pharmacies and hospitals.
Display omitted
Three-dimensional (3D) printing is revolutionising how we envision manufacturing in the pharmaceutical field. Here, we report for the first time the use of direct powder extrusion 3D ...printing: a novel single-step printing process for the production of printlets (3D printed tablets) directly from powdered materials. This new 3D printing technology was used to prepare amorphous solid dispersions of itraconazole using four different grades of hydroxypropylcellulose (HPC – UL, SSL, SL and L). All of the printlets showed good mechanical and physical characteristics and no drug degradation. The printlets showed sustained drug release characteristics, with drug concentrations higher than the solubility of the drug itself. The printlets prepared with the ultra-low molecular grade (HPC – UL) showed faster drug release compared with the other HPC grades, attributed to the fact that itraconazole was found in a higher percentage as an amorphous solid dispersion. This work demonstrates the potential of this innovate technology to overcome one of the major disadvantages of fused deposition modelling (FDM) 3D printing by avoiding the need for preparation of filaments by hot melt extrusion (HME). This novel single-step technology could revolutionise the preparation of amorphous solid dispersions as final formulations and it may be especially suited for preclinical studies, where the quantity of drugs is limited and without the need of using traditional HME.
Reshaping drug development using 3D printing Awad, Atheer; Trenfield, Sarah J.; Goyanes, Alvaro ...
Drug discovery today,
August 2018, 2018-08-00, 20180801, Letnik:
23, Številka:
8
Journal Article
Recenzirano
Odprti dostop
•3DP is forecast to become the single biggest disruptive technology to the global industry.•3DP is likely to cause a paradigm shift in pharmaceutical manufacture and supply.•3DP could be applied to ...the different phases of drug development.•The adoption of 3DP could raise several regulatory, legal and ethical considerations.
The pharmaceutical industry stands on the brink of a revolution, calling for the recognition and embracement of novel techniques. 3D printing (3DP) is forecast to reshape the way in which drugs are designed, manufactured, and used. Although a clear trend towards personalised fabrication is perceived, here we accentuate the merits and shortcomings of each technology, providing insights into aspects such as the efficiency of production, global supply, and logistics. Contemporary opportunities for 3DP in drug discovery and pharmaceutical development and manufacturing are unveiled, offering a forward-looking view on its potential uses as a digitised tool for personalised dispensing of drugs.
: Three-dimensional (3D) printing is a relatively new, rapid manufacturing technology that has found promising applications in the drug delivery and medical sectors. Arguably, never before has the ...healthcare industry experienced such a transformative technology. This review aims to discuss the state of the art of 3D printing technology in healthcare and drug delivery.
: The current and future applications of printing technologies within drug delivery and medicine have been discussed. The latest innovations in 3D printing of customized medical devices, drug-eluting implants, and printlets (3D-printed tablets) with a tailored dose, shape, size, and release characteristics have been covered. The review also covers the state of the art of 3D printing in healthcare (covering topics such as dentistry, surgical and bioprinting of patient-specific organs), as well as the potential of recent innovations, such as 4D printing, to shape the future of drug delivery and to improve treatment pathways for patients.
: A future perspective is provided on the potential for 3D printing in healthcare, covering strategies to overcome the major barriers to integration that are faced today.
Three-dimensional printing (3DP) has demonstrated great potential for multi-material fabrication because of its capability for printing bespoke and spatially separated material conformations. Such a ...concept could revolutionise the pharmaceutical industry, enabling the production of personalised, multi-layered drug products on demand. Here, we developed a novel stereolithographic (SLA) 3D printing method that, for the first time, can be used to fabricate multi-layer constructs (polypills) with variable drug content and/or shape. Using this technique, six drugs, including paracetamol, caffeine, naproxen, chloramphenicol, prednisolone and aspirin, were printed with different geometries and material compositions. Drug distribution was visualised using Raman microscopy, which showed that whilst separate layers were successfully printed, several of the drugs diffused across the layers depending on their amorphous or crystalline phase. The printed constructs demonstrated excellent physical properties and the different material inclusions enabled distinct drug release profiles of the six actives within dissolution tests. For the first time, this paper demonstrates the feasibility of SLA printing as an innovative platform for multi-drug therapy production, facilitating a new era of personalised polypills.
Display omitted
Three-dimensional printing (3DP) is a revolutionary technology in pharmaceuticals, enabling the personalisation of flexible-dose drug products and 3D printed polypills ...(polyprintlets). A major barrier to entry of this technology is the lack of non-destructive quality control methods capable of verifying the dosage of multiple drugs in polyprintlets at the point of dispensing. In the present study, 3D printed films and cylindrical polyprintlets were loaded with flexible, therapeutic dosages of two distinct drugs (amlodipine and lisinopril) across concentration ranges of 1–5% w/w and 2–10% w/w, respectively. The polyprintlets were non-destructively analysed for dose content using a portable near infrared (NIR) spectrometer and validated calibration models were developed using partial least squares (PLS) regression, which showed excellent linearity (R2 Pred = 0.997, 0.991), accuracy (RMSEP = 0.24%, 0.24%) and specificity (LV1 = 82.77%, 79.55%) for amlodipine and lisinopril, respectively. X-ray powder diffraction (XRPD) and thermogravimetric analysis (TGA) showed that sintering partially transformed the phase of both drugs from the crystalline to amorphous forms. For the first time, we report a non-destructive method for quality control of two separate active ingredients in a single 3D printed drug product using NIR spectroscopy, overcoming a major barrier to the integration of 3D printing into clinical practice.
Display omitted
Now more than ever, traditional healthcare models are being overhauled with digital technologies of Healthcare 4.0 increasingly adopted. Worldwide, digital devices are improving every ...stage of the patient care pathway. For one, sensors are being used to monitor patient metrics 24/7, permitting swift diagnosis and interventions. At the treatment stage, 3D printers are under investigation for the concept of personalised medicine by allowing patients access to on-demand, customisable therapeutics. Robots are also being explored for treatment, by empowering precision surgery, rehabilitation, or targeted drug delivery. Within medical logistics, drones are being leveraged to deliver critical treatments to remote areas, collect samples, and even provide emergency aid. To enable seamless integration within healthcare, the Internet of Things technology is being exploited to form closed-loop systems that remotely communicate with one another. This review outlines the most promising healthcare technologies and devices, their strengths, drawbacks, and opportunities for clinical adoption.
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.
PDF
