Search

Artificial intelligence (AI) encompasses a broad spectrum of techniques that have been utilized by pharmaceutical companies for decades, including machine learning, deep learning, and other advanced computational methods. These innovations have unlocked unprecedented opportunities for the acceleration of drug discovery and delivery, the optimization of treatment regimens, and the improvement of patient outcomes. AI is swiftly transforming the pharmaceutical industry, revolutionizing everything from drug development and discovery to personalized medicine, including target identification and validation, selection of excipients, prediction of the synthetic route, supply chain optimization, monitoring during continuous manufacturing processes, or predictive maintenance, among others. While the integration of AI promises to enhance efficiency, reduce costs, and improve both medicines and patient health, it also raises important questions from a regulatory point of view. In this review article, we will present a comprehensive overview of AI's applications in the pharmaceutical industry, covering areas such as drug discovery, target optimization, personalized medicine, drug safety, and more. By analyzing current research trends and case studies, we aim to shed light on AI's transformative impact on the pharmaceutical industry and its broader implications for healthcare. [ABSTRACT FROM AUTHOR]

Understanding the molecular mechanisms underlying the generation of absence seizures is crucial for developing effective, patient-specific treatments for childhood absence epilepsy (CAE). Currently, one-third of patients remain refractive to the antiseizure medications (ASMs), previously called antiepileptic drugs (AEDs), available to treat CAE. Additionally, these ASMs often produce serious side effects and can even exacerbate symptoms in some patients. Determining the precise cellular and molecular mechanisms directly responsible for causing this type of epilepsy has proven challenging as they appear to be complex and multifactorial in patients with different genetic backgrounds. Aberrant neuronal activity in CAE may be caused by several mechanisms that are not fully understood. Thus, dissecting the causal factors that could be targeted in the development of precision medicines without side effects remains a high priority and the ultimate goal in this field of epilepsy research. The aim of this review is to highlight our current understanding of potential causative mechanisms for absence seizure generation, based on the latest research using cutting-edge technologies. This information will be important for identifying potential targets for future therapeutic intervention. [ABSTRACT FROM AUTHOR]

Drug repurposing is a powerful tool for future medicine, through the process of discovering new uses for existing drugs. Drug repurposing drastically cuts the time and expense involved in developing new medications by utilizing safety profiles and efficacy data that are currently available. In a diverse population of humans, people have unique sets of inherited or non-inherited genetic abnormalities that result in certain individuals responding less or not to all general treatments or drugs. Medicines that have been approved may not be suitable for a person because of the deficiency of a specific target. This situation leads to the requirement of personalized medicines. Reduced lack of efficacy drug repurposing approach has a significant role, which results in best medicine accompanied by low toxicity and high efficacy. This is achieved together with the advancement of next-generation sequencing technologies and personalized genomic studies can be conducted with an affirmative approach. Prospects include advancements in artificial intelligence, big data analytics and other technologies, focusing on rare diseases, combining repurposed drugs with other medications or novel drugs, and in the development of personalized medicines. Drug repurposing is exciting and fast-developing and possesses the potential to completely change the pharmaceutical industry's approach to the development of medications. [ABSTRACT FROM AUTHOR]

Tissue regulatory T cells (Tregs) exert pivotal functions in both immune and metabolic regulation, maintaining local tissue homeostasis, integrity, and function. Accordingly, Tregs play a crucial role in controlling obesity-induced inflammation and supporting efficient muscle function and repair. Depending on the tissue context, Tregs are characterized by unique transcriptomes, growth, and survival factors and T cell receptor (TCR) repertoires. This functional specialization offers the potential to selectively target context-specific Treg populations, tailoring therapeutic strategies to specific niches, thereby minimizing potential side effects. Here, we discuss challenges and perspectives for niche-specific Treg targeting, which holds promise for highly efficient and precise medical interventions to combat metabolic disease. Becker and Dirschl et al. discuss challenges and perspectives for Treg-mediated control of metabolic tissues, highlighting the functional specialization of tissue Tregs. This specialization holds the future potential for precise interventions in metabolic diseases through niche-specific targeting of Tregs. [ABSTRACT FROM AUTHOR]

The immune system and cancer cells interact intricately during the growth of tumors, and the dynamic interplay between immune activation and suppression greatly influences the cancer outcome. Natural killer cells (NK), cytotoxic T lymphocytes (CTLs) and Dendritic cells (DC), employ diverse mechanisms, to combat cancer. However, the challenges posed by factors such as chronic inflammation and the immunosuppressive tumor microenvironment (TME) often hinder immune cells' ability to detect and eliminate tumors accurately. Immunotherapy offers a promising approach, reprogramming the immune system to target and eliminating cancer cells while minimizing side effects, enhancing immune memory, and lowering the risk of metastasis and relapse compared to traditional treatments like radiation and surgery. Nanotechnology presents a potential solution by enabling safer, more efficient drug delivery through nanoparticles. These nanoengineered drugs can be tailored for controlled activation and release. Improving TME characters holds potential for enhancing personalized immunotherapy and addressing T cell availability issues within tumor sites, particularly when combined with existing therapies. This review discusses TMEs and the strategies to overcome immunosuppression in TME, and various immune cell-based strategies to improve antitumor response. It also focuses on the strategies for constructing microenvironment responsive nanoplatforms based upon the factors present at higher levels in TME like acidic pH, hypoxia facilitated by poor oxygen supply, higher expression of certain enzymes, and other factors such light, ultrasound and magnetic field. Combination immune therapies combined with immunotherapy include photodynamic therapy, photothermal therapy, chemotherapy, gene therapy and radiotherapy, revealing a high level of anticancer activity in comparison to a single therapy, enhancing immunogenicity, promoting therapeutic efficacy, and lowering metastasis. In conclusion, cancer immunotherapy is a potential technique to combat cancer cells and boost the immune system, hindering their growth and recurrence. In order to prevent cancer, it helps the immune system target cancer cells selectively and strengthens its long-term memory. Clinical trials are extending the application of immunotherapy and identifying strategies to improve the immune system tumor-fighting capabilities. Immunotherapy has enormous promise and gives hope for more successful cancer treatment.

The technological developments associated with the branch of Radiation Oncology have been directed towards precise delivery of the dose, leading to improved survival in various solid malignancies. Radiation therapy as a treatment modality, is an integral component of more than half of the diagnosed malignancies. In spite of the role of adaptive radiation therapy evolving over the last decade, the fundamental question remains as to the difference in radiation response between individuals. Recently, the role of the radiosensitivity index has emerged, which has shown immense potential in the development of biologically driven tumor radiation therapy. The role of these novel methods of genome-based molecular assays needs to be explored to help in decision-making between radical treatment options for various malignancies and reduce the associated toxicity burden. In this article, we explore the current evidence available for various malignancy sites and provide a comprehensive review of the predictive values of various molecular markers available and their impact on the radiosensitivity index. [ABSTRACT FROM AUTHOR]

Additive manufacturing techniques, especially methods based on the deposition of thermoplastic material such as Fused deposition modeling (FDM), are gaining more and more applications. Due to the large variety of materials used and the quick ability to produce small batches of products in accordance with the computer project, these methods are considered as a method of dosage forms manufacturing both on an industrial scale as well as in small batches. Numerous scientific studies related to the printing of dosage forms of various structures have been published in recent years. These studies concern both preparations for oral administration, such as tablets and capsules with modified and immediate release of the active pharmaceutical ingredient (API), as well as intraocular dosage forms and wound dressings. In the case of the FDM method, the printing process is preceded by the material preparation step. It consists of the preparation of a drug-loaded filament in the hot-melt extrusion process. After feeding the filament into the printer's head, it is re-heated, liquefied, and precisely deposited on the printer's table in order to reproduce a spatial structure according to the computer design. The filaments used in the printing process of the dosage form should be characterized by, among others: appropriate mechanical strength, high diameter uniformity, and long-term stability. Apart from thermoplastic polymers, other excipients are also used in the composition of the formulation, i.e., disintegrants, plasticizers, and compounds inhibiting the API phase transformations in the polymer matrix. Printed dosage forms are often characterized by a complex internal spatial structure. For this reason, the API release depends not only on the properties of the excipients used, but especially on printouts’ surface area and porosity, as well as the shape and infill density. In addition, conditions during the extrusion and 3D printing processes may result in the dissolution of API in the polymer carrier and accelerate its dissolution rate.

The aim of this study is to investigate the influence of polymer chemistry on the properties of oral dosage forms produced using selective laser sintering (SLS). The dosage forms were printed using different grades of polyvinyl alcohol or copovidone in combination with indomethacin as the active pharmaceutical ingredient. The properties of the printed structures were assessed according to European Pharmacopoeia guidelines at different printing temperatures and laser scanning speeds in order to determine the suitable printing parameters.The results of the study indicate that the chemical properties of the polymers, such as dynamic viscosity, degree of hydrolyzation, and molecular weight, have significant impact on drug release and kinetics. Drug release rate and supersaturation can be modulated by selecting the appropriate polymer type. Furthermore, the physical properties of the dosage forms printed under the same settings are influenced by the selected polymer type, which determines the ideal manufacturing settings.This study demonstrates how the chemical properties of the polymer can determine the appropriate choice of manufacturing settings and the final properties of oral dosage forms produced using SLS.

Piezo/triboelectric nanogenerators (PTNGs) have become the research frontier in many cutting‐edge applications, which open up promising possibilities for broad prospects. Fiber materials are the ideal candidate for constructing high‐performance PTNGs owing to the compelling features of lightweight, programmable structure, favorable softness, and brilliant breathability. To this end, working mechanisms, material selections, structural designs and fabrication methods of fiber constructed PTNGs are comprehensively presented. An in‐depth analysis of emerging applications ranging from intelligent clothing, smart home, and personalized medicine to artificial intelligence is thoughtfully demonstrated. Furthermore, the current problems and potential challenges that hinder their large‐scale commercial applications are systematically discussed, laying emphasis on the future development direction of fiber constructed PTNGs. It is expected that this review will supply the audience with some universal strategies and fresh ideas to conduct deep research on fiber constructed PTNGs toward better performance. [ABSTRACT FROM AUTHOR]

Abstract Background The three-dimensional (3D) printing is paradigm shift in the healthcare sector. 3D printing is platform technologies in which complex products are developed with less number of additives. The easy development process gives edge over the conventional methods. Every individual needs specific dose treatment. ‘One size fits all’ is the current traditional approach that can shift to more individual specific in 3D printing. The present review aims to cover different perspectives regarding selection of drug, polymer and technological aspects for 3D printing. With respect to clinical practice, regulatory issue and industrial potential are also discussed in this paper. Main body The individualization of medicines with patient centric dosage form will become reality in upcoming future. It provides individual’s need of dose by considering genetic profile, physiology and diseased condition. The tailormade dosages with unique drug loading and release profile of different geometrical shapes and sizes can easily deliver therapeutic dose. The technology can fulfill growing demand of efficiency in the dose accuracy for the patient oriented sectors like pediatric, geriatric and also easy to comply with cGMP requirements of regulated market. The clinical practice can focus on prescribing each individual’s necessity of dose. Conclusion In the year 2015, FDA approved first 3D printed drug product, which is initiator in the new phase of manufacturing of pharmaceuticals. The tailormade formulations can be made in future for personalized medications. Regulatory approval from agencies can bring the 3DP product into the market. In the future, formulators can bring different sector-specific products for personalized need through 3DP pharmaceutical product. Graphical Abstract

[Display omitted] With the growing interest in environmentally friendly and personalized medicines, new concept for combining three-dimensional printing (3DP) with natural-based biomaterials derived from agro-food wastes has emerged. This approach provides sustainable solutions for agricultural waste management and potential for developing of novel pharmaceutical products with tunable characteristics. This work demonstrated the feasibility of fabricating personalized theophylline films with four different structures (Full, Grid, Star, and Hilbert) using syringe extrusion 3DP and carboxymethyl cellulose (CMC) derived from durian rind wastes. Our findings suggested that all the CMC-based inks with shear thinning properties capable of being extruded smoothly through a small nozzle could potentially be used to fabricate the films with various complex printing patterns and high structural fidelity. The results also demonstrated that the film characteristics and release profiles could be easily modified by simply changing the slicing parameters (e.g., infill density and printing pattern). Amongst all formulations, Grid film, which was 3D-printed with 40 % infill and a grid pattern, demonstrated a highly porous structure with high total pore volume. The voids between printing layers in Grid film increased theophylline release (up to 90 % in 45 min) through improved wetting and water penetration. All findings in this study provide significant insight into how to modify film characteristics simply by digitally changing the printing pattern in slicer software without creating a new CAD model. This approach could help to simplify the 3DP process so that non-specialist users can easily implement it in community pharmacies or hospital on demand. [ABSTRACT FROM AUTHOR]

3D printing technologies enable medicine customization adapted to patients' needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines. 3D-printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained-release 3D-printed implants, stents, and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines, such as wound dressing, microneedles, and medicated contact lenses, have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing technique most suitable for each application and the type of pharmaceutical ink that should be developed that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing ("nanoprinting") brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice. [ABSTRACT FROM AUTHOR]

Niclosamide (NCS) is a drug that has been used as an anthelmintic and anti-parasitic drug for about 40 years. Recently, some studies have highlighted its potential in treating various tumors, allowing a repositioning of this drug. Despite its potential, NCS is a Biopharmaceutical Classification System (BCS) Class II drug and is consequently characterized by low aqueous solubility, poor dissolution rate and reduced bioavailability, which limits its applicability. In this work, we utilize a very novel technique, direct powder extrusion (DPE) 3D printing, which overcomes the limitations of previously used techniques (fused deposition modelling, FDM) to achieve direct extrusion of powder mixtures consisting of NCS, hydroxypropyl methylcellulose (HPMC, Affinisol 15 LV), hydroxypropyl-β-cyclodextrin (HP-β-CD) and polyethylene glycol (PEG) 6000. For the first time, direct printing of powder blends containing HP-β-CD was conducted. For all tablets, in vitro dissolution studies showed sustained drug release over 48 h, but for tablets containing HP-β-CD, the release was faster. Solid-state characterization studies showed that during extrusion, the drug lost its crystal structure and was evenly distributed within the polymer matrix. All printed tablets have exhibited good mechanical and physical features and a stability of the drug content for up to 3 months. This innovative printing technique has demonstrated the possibility to produce personalized pharmaceutical forms directly from powders, avoiding the use of filament used by FDM. [ABSTRACT FROM AUTHOR]

Nanotechnology has revolutionized the field of biomedical sciences with smart approaches of imaging and treatment. This transformation has led to the development of a new field named 'nanomedicine', which has provided prospects for personalized medicines and offers hope for some rare diseases. In this context, the ability to manipulate various nanomaterials to suit diverse applications is a characteristic feature which has gained popularity. Nevertheless, the toxicity exerted by the nanomaterials has limited their lab-to-bench translations. Moreover, the noxiousness of nanomaterials has paved the emergence of another dedicated field named 'nanotoxicology'. Therefore, it is essential to control nanomaterials' toxicity and engineer nanomaterials with smart approaches for selective biomedical actions. Here we review engineered nanomaterials including metal and metal oxide, semiconductor, carbon-based, polymeric, and biological-based nanomaterials, and their potential applications in managing microbes, regenerative medicine, tissue engineering, dentistry, cancer treatment, personalized medications, and neglected rare diseases. We discuss the origin of nanotoxicity and how it is influenced by physicochemical properties of nanomaterials, synthesis methods, routes of administration, nano-bio-interface, and choice of the cell lines employed in the assessment. At the end, we discuss strategies and regulations adopted to mitigate the nanotoxicological concerns with future perspectives. [ABSTRACT FROM AUTHOR]

The immune system and cancer cells interact intricately during the growth of tumors, and the dynamic interplay between immune activation and suppression greatly influences the cancer outcome. Natural killer cells (NK), cytotoxic T lymphocytes (CTLs) and Dendritic cells (DC), employ diverse mechanisms, to combat cancer. However, the challenges posed by factors such as chronic inflammation and the immunosuppressive tumor microenvironment (TME) often hinder immune cells' ability to detect and eliminate tumors accurately. Immunotherapy offers a promising approach, reprogramming the immune system to target and eliminating cancer cells while minimizing side effects, enhancing immune memory, and lowering the risk of metastasis and relapse compared to traditional treatments like radiation and surgery. Nanotechnology presents a potential solution by enabling safer, more efficient drug delivery through nanoparticles. These nanoengineered drugs can be tailored for controlled activation and release. Improving TME characters holds potential for enhancing personalized immunotherapy and addressing T cell availability issues within tumor sites, particularly when combined with existing therapies. This review discusses TMEs and the strategies to overcome immunosuppression in TME, and various immune cell-based strategies to improve antitumor response. It also focuses on the strategies for constructing microenvironment responsive nanoplatforms based upon the factors present at higher levels in TME like acidic pH, hypoxia facilitated by poor oxygen supply, higher expression of certain enzymes, and other factors such light, ultrasound and magnetic field. Combination immune therapies combined with immunotherapy include photodynamic therapy, photothermal therapy, chemotherapy, gene therapy and radiotherapy, revealing a high level of anticancer activity in comparison to a single therapy, enhancing immunogenicity, promoting therapeutic efficacy, and lowering metastasis. In conclusion, cancer immunotherapy is a potential technique to combat cancer cells and boost the immune system, hindering their growth and recurrence. In order to prevent cancer, it helps the immune system target cancer cells selectively and strengthens its long-term memory. Clinical trials are extending the application of immunotherapy and identifying strategies to improve the immune system tumor-fighting capabilities. Immunotherapy has enormous promise and gives hope for more successful cancer treatment., (© 2024 The Author(s). Published by IMR Press.)

3D printing technologies enable medicine customization adapted to patients’ needs. There are several 3D printing techniques available, but majority of dosage forms and medical devices are printed using nozzle-based extrusion, laser-writing systems, and powder binder jetting. 3D printing has been demonstrated for a broad range of applications in development and targeting solid, semi-solid, and locally applied or implanted medicines. 3D-printed solid dosage forms allow the combination of one or more drugs within the same solid dosage form to improve patient compliance, facilitate deglutition, tailor the release profile, or fabricate new medicines for which no dosage form is available. Sustained-release 3D-printed implants, stents, and medical devices have been used mainly for joint replacement therapies, medical prostheses, and cardiovascular applications. Locally applied medicines, such as wound dressing, microneedles, and medicated contact lenses, have also been manufactured using 3D printing techniques. The challenge is to select the 3D printing technique most suitable for each application and the type of pharmaceutical ink that should be developed that possesses the required physicochemical and biological performance. The integration of biopharmaceuticals and nanotechnology-based drugs along with 3D printing (“nanoprinting”) brings printed personalized nanomedicines within the most innovative perspectives for the coming years. Continuous manufacturing through the use of 3D-printed microfluidic chips facilitates their translation into clinical practice.

3D printing has emerged as an advanced manufacturing technology in the field of pharmaceutical sciences. Despite much focus on enteral applications, there has been a lack of research focused on potential benefits of 3D printing for parenteral applications such as wound dressings, biomedical devices, and regenerative medicines. 3D printing technologies, including fused deposition modeling, vat polymerization, and powder bed printing, allow for rapid prototyping of personalized medications, capable of producing dosage forms with flexible dimensions based on patient anatomy as well as dosage form properties such as porosity. Considerations such as printing properties and material selection play a key role in determining overall printability of the constructs. These parameters also impact drug release kinetics, and mechanical properties of final printed constructs, which play a role in modulating immune response upon insertion in the body. Despite challenges in sterilization of printed constructs, additional post-printing processing procedures, and lack of regulatory guidance, 3D printing will continue to evolve to meet the needs of developing effective, personalized medicines for parenteral applications. [ABSTRACT FROM AUTHOR]

The last twenty years of seminal microbiome research has uncovered microbiota’s intrinsic relationship with human health. Studies elucidating the relationship between an unbalanced microbiome and disease are currently published daily. As such, microbiome big data have become a reality that provide a mine of information for the development of new therapeutics. Machine learning (ML), a branch of artificial intelligence, offers powerful techniques for big data analysis and prediction-making, that are out of reach of human intellect alone. This review will explore how ML can be applied for the development of microbiome-targeted therapeutics. A background on ML will be given, followed by a guide on where to find reliable microbiome big data. Existing applications and opportunities will be discussed, including the use of ML to discover, design, and characterize microbiome therapeutics. The use of ML to optimize advanced processes, such as 3D printing and in silico prediction of drug-microbiome interactions, will also be highlighted. Finally, barriers to adoption of ML in academic and industrial settings will be examined, concluded by a future outlook for the field.

Precision polymers as advanced nanomedicines represent an appealing approach for the treatment of otherwise untreatable malignancies. By taking advantage of unique nanomaterial properties and implementing judicious design strategies, polymeric nanomedicines are able to be produced that overcome many barriers to effective treatment. Current key research focus areas anticipated to produce the greatest impact in polymer applications in nanomedicine for oncology include new strategies to achieve "active" targeting, polymeric pro‐drug activation, and combinatorial polymer drug delivery approaches in combination with enhanced understanding of complex bio‐nano interactions. These approaches, both in isolation or combination, form the next generation of precision nanomedicines with significant anticipated future health outcomes. Of necessity, these approaches will combine an intimate understanding of biological interactions with advanced materials design. This perspectives piece aims to highlight emerging opportunities that promise to be game changers in the nanomedicine oncology field. Discussed herein are current and next generation polymeric nanomedicines with a focus towards structures that are, or could, undergo clinical translation as well as highlight key advances in the field. [ABSTRACT FROM AUTHOR]

[Display omitted] • This review offers a comprehensive examination of the various facets of 3D printing technology as it applies to pharmaceuticals. • Specifically, the analysis focuses on the use of 3D printing to create personalized medications for pediatric patients. • The study provides a solid theoretical foundation for the use of 3D printing in clinical settings. • Additionally, it delves into the pros and cons of using this technology to create pediatric. In recent years, the rapid advancement of three-dimensional (3D) printing technology has yielded distinct benefits across various sectors, including pharmaceuticals. The pharmaceutical industry has particularly experienced advantages from the utilization of 3D-printed medications, which have invigorated the development of tailored drug formulations. The approval of 3D-printed drugs by the U.S. Food and Drug Administration (FDA) has significantly propelled personalized drug delivery. Additionally, 3D printing technology can accommodate the precise requirements of pediatric drug dosages and the complexities of multiple drug combinations. This review specifically concentrates on the application of 3D printing technology in pediatric preparations, encompassing a broad spectrum of uses and refined pediatric formulations. It compiles and evaluates the fundamental principles associated with the application of 3D printing technology in pediatric preparations, including its merits and demerits, and anticipates its future progression. The objective is to furnish theoretical underpinning for 3D printing technology to facilitate personalized drug delivery in pediatrics and to advocate for its implementation in clinical settings. [ABSTRACT FROM AUTHOR]

Customized pharmaceutical products aim to comply with the individual needs of a patient to enhance the treatment outcome. The current pharmaceutical production paradigm is, however, dominated by mass production, where the pharmaceutical products embrace a one-size-fits-all design with a low possibility of treatment optimization to patient needs. This production paradigm is not designed or intended for customized pharmaceutical products and operating this production context for customized pharmaceutical products is argued to be cost-inefficient. To address this challenge of inefficient production of customized pharmaceutical products, this study proposes an approach to modular pharmaceutical product design. As a mass customization strategy, product modularization enables serving customers with customized products cost-efficiently. The proposed modular pharmaceutical products integrate three product design requirements originating from patient needs: a scalable dose strength, a flexible target release profile, and a scalable treatment size. An approach to assess the value of these product designs is presented, by means of proposing three benefit metrics complying with respective design requirements and a cost metric assessing the cost of producing these modular pharmaceutical product designs. Results suggest that pharmaceutical product modularization can, by keeping the number of produced components low, substantially increase the external product variety and, hence, enhance the treatment outcome of patients. Furthermore, results indicate that the achieved benefit for the patient through product modularization increases beyond additional costs arising during production. However, a careful modularization must be performed to optimize the tradeoff between the increased benefit and cost.

Layer-by-layer fabrication of three dimensional (3D) objects from digital models is called 3D printing. This technology established just about three decades ago at the confluence of materials science, chemistry, robotics, and optics researches to ease the fabrication of UV-cured resin prototypes. The 3D technology was rapidly considered as a standard instrument in the aerospace, automotive, and consumer goods production factories. Nowadays, research interests in the 3D printed products have been raised and achieved ever-increasing traction in the pharmaceutical industry; so that, the first 3D printed drug product was approved by FDA in August 2015. This editorial summarizes the competitive advantages of the 3D printing for the made-on-demand, personalized and complex products, manufacturing of which establish opportunities for enhancing the accessibility, effectiveness, and safety of drugs.

The objective of the work is to recognize the recent advancements in the modern health care and drug delivery systems. The article describes few recent developments in technology like artificial intelligence, personalized medicines, customized medicines, 3D printing, bioelectronic devices and tele pharmacy, which have the potential to augment health care and drug delivery in coming times. Personalized medication ensures precise health care as per the individual genetic makeup of the patients. The 3D printing technology enables to deliver tailor made solutions to fulfil individual patient requirements. Bioelectronic medicines and devices are new technology where the patient wears a device and its electrical signal cures certain ailments. Tele pharmacy ensures that the technological advances of telecommunications are also passed on to the patient health care sector. Moreover, it can be said that all these modern developments ensure that the quality of life improves and there comes a better control on the health care costs. [ABSTRACT FROM AUTHOR]

In this study, the possibility of producing pharmaceutical dosage forms by 3D printing technology is examined. In vitro dissolution tests were performed with printed dosage forms, and the results analysed in Microsoft Excel Add-In, DDSolver. 3D printing has provided six different models of solid dosage forms. The results of dissolution test have shown release profiles with initial time delay. The profiles are described by the Peppas-Sahlin model. It is shown that 3D printing technology has the potential to become a method for quick and simple production of personalized dosage forms with delayed release. [ABSTRACT FROM AUTHOR]

Three-dimensional printing (3DP) has gained popularity among scientists and researchers in every field due to its potential to drastically reduce energy costs for the production of customised products by utilising less energy-intensive machines as well as minimising material waste. The 3D printing technology is an additive manufacturing approach that uses material layer-by-layer fabrication to produce the digitally specified 3D model. The use of 3D printing technology in the pharmaceutical sector has the potential to revolutionise research and development by providing a quick and easy means to manufacture personalised one-off batches, each with unique dosages, distinct substances, shapes, and sizes, as well as variable release rates. This overview addresses the concept of 3D printing, its evolution, and its operation, as well as the most popular types of 3D printing processes utilised in the health care industry. It also discusses the application of these cutting-edge technologies to the pharmaceutical industry, advancements in various medical fields and medical equipment, 3D bioprinting, the most recent initiatives to combat COVID-19, regulatory frameworks, and the major challenges that this technology currently faces. In addition, we attempt to provide some futuristic approaches to 3DP applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Graphical abstract Abstract Hypothyroidism is a chronic and debilitating disease that is estimated to affect 3% of the general population. Clinical experience has highlighted the synergistic value of combining triiodothyronine (T 3 ) and thyroxine (T 4 ) for persistent or recurrent symptoms. However, thus far a platform that enables the simultaneous and independent dosing of more than one drug for oral administration has not been developed. Thermal inkjet (TIJ) 2D printing is a potential solution to enable the dual deposition of T 3 and T 4 onto orodispersible films (ODFs) for therapy personalisation. In this study, a two-cartridge TIJ printer was modified such that it could print separate solutions of T 3 and T 4. Dose adjustments were achieved by printing solutions adjacent to each other, enabling therapeutic T 3 (15–50 μg) and T 4 dosages (60–180 μg) to be successfully printed. Excellent linearity was observed between the theoretical and measured dose for both T 3 and T 4 (R2 = 0.982 and 0.985, respectively) by changing the length of the print objective (Y-value). Rapid disintegration of the ODFs was achieved (<45 s). As such, this study for the first time demonstrates the ability to produce personalised dose combinations by TIJ printing T 3 and T 4 onto the same substrate for oral administration. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Three-dimensional printing (3DP) is gaining momentum in the field of pharmaceuticals, offering innovative opportunities for medicine manufacture. Selective laser sintering (SLS) is a novel, high resolution and single-step printing technology that we have recently introduced to the pharmaceutical sciences. The aim of this work was to use SLS 3DP to fabricate printlets (3D printed tablets) with cylindrical, gyroid lattice and bi-layer structures having customisable release characteristics. Paracetamol-loaded constructs from four different pharmaceutical grade polymers including polyethylene oxide, Eudragit (L100-55 and RL) and ethyl cellulose, were created using SLS 3DP. The novel gyroid lattice structure was able to modulate the drug release from all four polymers. This work is the first to demonstrate the feasibility of using SLS to achieve customised drug release properties of several polymers, in a swift, cost-effective manner, avoiding the need to alter the formulation composition. By creating these constructs, it is therefore possible to modify drug release, which in practice, could enable the tailoring of drug performance to the patient simply by changing the 3D design. [ABSTRACT FROM AUTHOR]

The aim of this work was to explore the feasibility of using selective laser sintering (SLS) 3D printing (3DP) to fabricate orodispersable printlets (ODPs) containing ondansetron. Ondansetron was first incorporated into drug-cyclodextrin complexes and then combined with the filler mannitol. Two 3D printed formulations with different levels of mannitol were prepared and tested, and a commercial ondansetron orally disintegrating tablet (ODT) product (Vonau® Flash) was also investigated for comparison. Both 3D printed formulations disintegrated at ~15 s and released more than 90% of the drug within 5 min independent of the mannitol content; these results were comparable to those obtained with the commercial product. This work demonstrates the potential of SLS 3DP to fabricate orodispersible printlets with characteristics similar to a commercial ODT, but with the added benefit of using a manufacturing technology able to prepare medicines individualized to the patient.

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.

The pharmaceutical industry is set to join the fourth industrial revolution with the 3D printing of medicines. The application of 3D printers in compounding pharmacies will turn them into digital pharmacies, wrapping up the telemedicine care cycle and definitively modifying the pharmacotherapeutic treatment of patients. Fused deposition modeling 3D printing technology melts extruded drug-loaded filaments into any dosage form; and allows the obtainment of flexible dosages with different shapes, multiple active pharmaceutical ingredients and modulated drug release kinetics—in other words, offering customized medicine. This work aimed to present an update on this technology, discussing its challenges. The co-participation of the pharmaceutical industry and compounding pharmacies seems to be the best way to turn this technology into reality. The pharmaceutical industry can produce drug-loaded filaments on a large scale with the necessary quality and safety guarantees; while digital pharmacies can transform the filaments into personalized medicine according to specific prescriptions. For this to occur, adaptations in commercial 3D printers will need to meet health requirements for drug products preparation, and it will be necessary to make advances in regulatory gaps and discussions on patent protection. Thus, despite the conservatism of the sector, 3D drug printing has the potential to become the biggest technological leap ever seen in the pharmaceutical segment, and according to the most optimistic prognostics, it will soon be within reach.

Patient-centric medicine is a derivative term for personalised medicine, whereby the pharmaceutical product provides the best overall benefit by meeting the comprehensive needs of the individual; considering the end-user from the beginning of the formulation design process right through development to an end product is a must. One way in which to obtain personalised medicines, on-site and on-demand is by three-dimensional printing (3DP). The aim of this study was to investigate the influence of the shape, size and colour of different placebo 3D printed tablets (Printlets™) manufactured by fused deposition modelling (FDM) 3DP on end-user acceptability regarding picking and swallowing. Ten different printlet shapes were prepared by 3DP for an open-label, randomised, exploratory pilot study with 50 participants. Participant-reported outcome (PRO) and researcher reported outcome (RRO) were collected after picking and swallowing of selected printlet geometries including sphere, torus, disc, capsule and tilted diamond shapes. The torus printlet received the highest PRO cores for ease of swallowing and ease of picking. Printlets with a similar appearance to conventional formulations (capsule and disc shape) were also found to be easy to swallow and pick which demonstrates that familiarity is a critical acceptability attribute for end-users. RRO scores were in agreement with the PRO scores. The sphere was not perceived to be an appropriate way of administering an oral solid medicine. Smaller printlet sizes were found to be preferable; however it was found that the perception of size was driven by the type of shape. Printlet colour was also found to affect the perception of the end-user. Our study is the first to guide the pharmaceutical industry towards developing patient-centric medicine in different geometries via 3DP. Overall, the highest acceptability scores for torus printlets indicates that FDM 3DP is a promising fabrication technology towards increasing patient acceptability of solid oral medicines. [ABSTRACT FROM AUTHOR]

Selective laser sintering (SLS) 3-dimensional printing is currently used for industrial manufacturing of plastic, metallic and ceramic objects. To date there have been no reports on the use of SLS to fabricate oral drug loaded products; therefore, the aim of this work was to explore the suitability of SLS printing for manufacturing medicines. Two thermoplastic pharmaceutical grade polymers, Kollicoat IR (75% polyvinyl alcohol and 25% polyethylene glycol copolymer) and Eudragit L100-55 (50% methacrylic acid and 50% ethyl acrylate copolymer), with immediate and modified release characteristics respectively, were selected to investigate the versatility of a SLS printer. Each polymer was investigated with three different drug loadings of paracetamol (acetaminophen) (5, 20 and 35%). To aid the sintering process, 3% Candurin ® gold sheen was added to each of the powdered formulations. In total, six solid formulations were successfully printed; the printlets (3D printed tablets) were robust, and no evidence of drug degradation was observed. In biorelevant bicarbonate dissolution media, the Kollicoat formulations showed pH-independent release characteristics, with the release rate dependent on the drug content. In the case of the Eudragit formulations, these showed pH-dependent, modified-release profiles independent of drug loading, with complete release being achieved over 12 h. In conclusion, this work has demonstrated that SLS is a versatile and practical 3D printing technology which can be applied to the pharmaceutical field, thus widening the armamentarium of 3D printing technologies available for the manufacture of modern medicines. [ABSTRACT FROM AUTHOR]

The aim of this study was to manufacture 3D printed tablets (printlets) from enteric polymers by single filament fused deposition modeling (FDM) 3D printing (3DP). Hot melt extrusion was used to generate paracetamol-loaded filaments from three different grades of the pharmaceutical excipient hypromellose acetate succinate (HPMCAS), grades LG, MG and HG. One-step 3DP was used to process these filaments into enteric printlets incorporating up to 50% drug loading with two different infill percentages (20 and 100%). X-ray Micro Computed Tomography (Micro-CT) analysis revealed that printlets with 20% infill had cavities in the core compared to 100% infill, and that the density of the 50% drug loading printlets was higher than the equivalent formulations loaded with 5% drug. In biorelevant bicarbonate dissolution media, drug release from the printlets was dependent on the polymer composition, drug loading and the internal structure of the formulations. All HPMCAS-based printlets showed delayed drug release properties, and in the intestinal conditions, drug release was faster from the printlets prepared with polymers with a lower pH-threshold: HPMCAS LG > HPMCAS MG > HPMCAS HG. These results confirm that FDM 3D printing makes it possible not only to manufacture delayed release printlets without the need for an outer enteric coating, but it is also feasible to adapt the release profile in response to the personal characteristics of the patient, realizing the full potential of additive manufacturing in the development of personalised dose medicines. [ABSTRACT FROM AUTHOR]