3D printed infliximab suppositories for rectal biologic delivery

Infliximab is a monoclonal antibody that plays an important role in the management and treatment of chronic inflammatory bowel diseases (IBD). Due to its macromolecular structure, its delivery through the oral route is challenging, limiting its administration to only via the parenteral route. The rectal route offers an alternative way for administering infliximab, allowing it to be localised at the disease site and circumventing its passage across the alimentary canal and thus, maintaining its integrity and bioactivity. Three-dimensional (3D) printing is an advanced production technology that permits the creation of dose-flexible drug products from digital designs. The current study assessed the feasibility of utilising semi-solid extrusion 3D printing for the fabrication of infliximab-loaded suppositories for the local treatment of IBD. Various printing inks composed of Gelucire® (48/16 or 44/14) mixed with coconut oil and/or purified water were investigated. It was shown that following reconstitution in water, the infliximab solution can be directly incorporated into the printing ink of Gelucire® 48/16 and can withstand the extrusion process, resulting in well-defined suppositories. Since water content and temperature are critical for safeguarding infliximab's potency, the effect of changing the composition of the printing inks and printing parameters on infliximab's biologic efficiency was evaluated by measuring its binding capacity (i.e., the amount of infliximab that actively binds to its antigen to exert an effect). Despite drug loading assays showing that infliximab remains intact following printing, it was found that the incorporation of water in isolation results in only ∼65% binding capacity. However, when oil is added to the mixture, infliximab's binding capacity increases up to ∼85%. These promising results demonstrate that 3D printing has the potential to be exploited as a novel platform for fabricating dosage forms containing biopharmaceuticals, avoiding patients' compliance issues observed with injectables and addressing their unmet needs

Advances in powder bed fusion 3D printing in drug delivery and healthcare

Powder bed fusion (PBF) is a 3D printing method that selectively consolidates powders into 3D objects using a power source. PBF has various derivatives; selective laser sintering/melting, direct metal laser sintering, electron beam melting and multi-jet fusion. These technologies provide a multitude of benefits that make them well suited for the fabrication of bespoke drug-laden formulations, devices and implants. This includes their superior printing resolution and speed, and ability to produce objects without the need for secondary supports, enabling them to precisely create complex products. Herein, this review article outlines the unique applications of PBF 3D printing, including the main principles underpinning its technologies and highlighting their novel pharmaceutical and biomedical applications. The challenges and shortcomings are also considered, emphasising on their effects on the 3D printed products, whilst providing a forward-thinking view

Reshaping drug development using 3D printing

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 digitized tool for personalised dispensing of drugs

3D printing: Principles and pharmaceutical applications of selective laser sintering

Pharmaceutical three-dimensional (3D) printing is a modern fabrication process with the potential to create bespoke drug products of virtually any shape and size from a computer-aided design model. Selective laser sintering (SLS) 3D printing combines the benefits of high printing precision and capability, enabling the manufacture of medicines with unique engineering and functional properties. This article reviews the current state-of-the-art in SLS 3D printing, including the main principles underpinning this technology, and highlights the diverse selection of materials and essential parameters that influence printing. The technical challenges and processing conditions are also considered in the context of their effects on the printed product. Finally, the pharmaceutical applications of SLS 3D printing are covered, providing an emphasis on the advantages the technology offers to drug product manufacturing and personalised medicine

Vat photopolymerization 3D printing for advanced drug delivery and medical device applications

Three-dimensional (3D) printing is transforming manufacturing paradigms within healthcare. Vat photopolymerization 3D printing technology combines the benefits of high resolution and favourable printing speed, offering a sophisticated approach to fabricate bespoke medical devices and drug delivery systems. Herein, an overview of the vat polymerization techniques, their unique applications in the fields of drug delivery and medical device fabrication, material examples and the advantages they provide within healthcare, is provided. The outstanding challenges and drawbacks presented by this technology are also discussed. It is forecast that the adoption of 3D printing could pave the way for a personalised health system, advancing from traditional treatments pathways towards digital healthcare and streamlining a new cyber era

3D printed multi-drug-loaded suppositories for acute severe ulcerative colitis

Acute severe ulcerative colitis (ASUC) is a growing health burden that often requires treatment with multiple therapeutic agents. As inflammation is localised in the rectum and colon, local drug delivery using suppositories could improve therapeutic outcomes. Three-dimensional (3D) printing is a novel manufacturing tool that permits the combination of multiple drugs in personalised dosage forms, created based on each patient's disease condition. This study, for the first time, demonstrates the feasibility of producing 3D printed suppositories with two anti-inflammatory agents, budesonide and tofacitinib citrate, for the treatment of ASUC. As both drugs are poorly water-soluble, the suppositories' ability to self-emulsify was exploited to improve their performance. The suppositories were fabricated via semi-solid extrusion (SSE) 3D printing and contained tofacitinib citrate and budesonide in varying doses (10 or 5 mg; 4 or 2 mg, respectively). The suppositories displayed similar dissolution and disintegration behaviours irrespective of their drug content, demonstrating the flexibility of the technology. Overall, this study demonstrates the feasibility of using SSE 3D printing to create multi-drug suppositories for the treatment of ASUC, with the possibility of titrating the drug doses based on the disease progression

3D Printed Tablets (Printlets) with Braille and Moon Patterns for Visually Impaired Patients

Visual impairment and blindness affects 285 million people worldwide, resulting in a high public health burden. This study reports, for the first time, the use of three-dimensional (3D) printing to create orally disintegrating printlets (ODPs) suited for patients with visual impairment. Printlets were designed with Braille and Moon patterns on their surface, enabling patients to identify medications when taken out of their original packaging. Printlets with different shapes were fabricated to offer additional information, such as the medication indication or its dosing regimen. Despite the presence of the patterns, the printlets retained their original mechanical properties and dissolution characteristics, wherein all the printlets disintegrated within ~5 s, avoiding the need for water and facilitating self-administration of medications. Moreover, the readability of the printlets was verified by a blind person. Overall, this novel and practical approach should reduce medication errors and improve medication adherence in patients with visual impairment

Smartphone-enabled 3D printing of medicines

3D printing is a manufacturing technique that is transforming numerous industrial sectors, particularly where it is key tool in the development and fabrication of medicinees that are personalised to the individual needs of patients. Most 3D printers are relatively large, require trained operators and must be located in a pharmaceutical setting to manufacture dosage forms. In order to realise fully the potential of point-of-care manufacturing of medicines, portable printers that are easy to operate are required. Here, we report the development of a 3D printer that operates using a mobile smartphone. The printer, operating on stereolithographic principles, uses the light from the smartphone’s screen to photopolymerise liquid resins and create solid structures. The shape of the printed dosage form is determined using a custom app on the smartphone. Warfarin-loaded Printlets (3D printed tablets) of various sizes and patient-centred shapes (caplet, triangle, diamond, square, pentagon, torus, and gyroid lattices) were successfully printed to a high resolution and with excellent dimensional precision using different photosensitive resins. The drug was present in an amorphous form, and the Printlets displayed sustained release characterises. The promising proof-of-concept results support the future potential of this compact, user-friendly and interconnected smartphone-based system for point-of-care manufacturing of personalised medications

3D printed opioid medicines with alcohol-resistant and abuse-deterrent properties

In the past decade, prescriptions for opioid medicines have been exponentially increasing, instigating opioid abuse as a global health crisis associated with high morbidity and mortality. In particular, diversion from the intended mode of opioid administration, such as injecting and snorting the opioid, is a major problem that contributes to this epidemic. In light of this, novel formulation strategies are needed to support efforts in reducing the prevalence and risks of opioid abuse. Here, modified release tramadol printlets (3D printed tablets) with alcohol-resistant and abuse-deterrent properties were prepared by direct powder extrusion three-dimensional printing. The printlets were fabricated using two grades of hydroxypropylcellulose (HPC). Both formulations displayed strong alcohol-resistance and had moderate abuse-deterrent properties. Polyethylene oxide (PEO) was subsequently added into the formulations, which improved the printlets' resistance to physical tampering in nasal inhalation tests and delayed their dissolution in solvent extraction tests. Overall, this article reports for the first time the use of direct powder extrusion three-dimensional printing to prepare drug products with both alcohol-resistant and abuse-deterrent properties. These results offer a novel approach for the safe and effective use of opioids that can be combined with the advantages that 3D printing provides in terms of on-demand dose personalisation

Shaping the future: recent advances of 3D printing in drug delivery and healthcare

Introduction: 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. Areas covered: 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. Expert opinion: 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