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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., Competing Interests: Jonas Lindh reports financial support was provided by Sweden's Innovation Agency. Maria Stromme reports financial support was provided by Swedish Research Council. Jonas Lindh reports financial support was provided by Merck KGaA. Maria Stromme reports financial support was provided by Erling Persson Family Foundation., (© 2023 Published by Elsevier B.V.)

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-ondemand, personalized and complex products, manufacturing of which establish opportunities for enhancing the accessibility, effectiveness, and safety of drugs. [ABSTRACT FROM AUTHOR]

[Display omitted] The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40 hydrogenated castor oil), Poloxamer 188 (2-methyloxirane) and Tween 80 (polyoxyethylene (80) sorbitan monooleate) were screened at 0.07 – 5% concentrations for their effect on ranitidine bioavailability in male and female Wistar rats. We show that all excipient concentrations significantly increased ranitidine bioavailability in male, but not female, rats. The effect of these excipients on the intestinal efflux transporters P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and multi-drug resistant protein 2 (MRP2) were also monitored. Measured by ELISA assay, in male rats, peak reductions in intestinal P-gp protein expression occurred in the presence of 1% Cremophor RH 40 and Poloxamer 188 and 0.5% Tween 80. In contrast, no distinct changes were observed in female intestinal P-gp expression. Unlike P-gp, all excipients had a positive effect on MRP2 protein expression – albeit only in males – in a concentration-dependent manner. The excipients did not modulate intestinal BCRP protein expression in either sex. Endogenous hormones and a nuclear receptor (testosterone, oestradiol and pregnane X receptor; PXR) that are purported to regulate intestinal efflux membrane transporter expression were also quantified. In the presence of all excipients, testosterone levels significantly elevated in males, although PXR levels reduced at similar rates in both sexes. No significant effects were identified in oestradiol levels in male and female rats. It is clear that excipients are not inert and their pathway for modulating drug response is multi-dimensional and specific between sexes. This study showed that excipients increased drug bioavailability of a P-gp drug substrate due to its reductive effect on intestinal P-gp expression; we propose that this link may be due to the excipients modulating fundamental testosterone levels. Understanding the implication of excipients on intestinal physiology and hormone levels can therefore improve pharmaceutical design, clinical efficacy and instigate next generation personalised, sex-specific formulations. [ABSTRACT FROM AUTHOR]

We develop a conceptual framework for estimating the value of personalized medicines. We show that personalizing medicines generates value from two sources. The first is a market-expansion effect by persons who initiate treatment due to reduced pre-treatment uncertainty about the effectiveness or side effects of treatment. The second is a market-contraction effect due to discontinuation of treatment by persons unresponsive to treatment. We apply the conceptual framework to evaluate the value of a predictive test to assess whether patients are at elevated risk for cardiac complications from COX-2 inhibitors. We find that this predictive test would yield an overall value to patients of about $16 billion per year or $1284 per likely patient. [ABSTRACT FROM AUTHOR]

Abstract: Cell-free protein synthesis has emerged as a powerful technology platform to help satisfy the growing demand for simple and efficient protein production. While used for decades as a foundational research tool for understanding transcription and translation, recent advances have made possible cost-effective microscale to manufacturing scale synthesis of complex proteins. Protein yields exceed grams protein produced per liter reaction volume, batch reactions last for multiple hours, costs have been reduced orders of magnitude, and reaction scale has reached the 100-liter milestone. These advances have inspired new applications in the synthesis of protein libraries for functional genomics and structural biology, the production of personalized medicines, and the expression of virus-like particles, among others. In the coming years, cell-free protein synthesis promises new industrial processes where short protein production timelines are crucial as well as innovative approaches to a wide range of applications. [Copyright &y& Elsevier]

Purpose: To evaluate the use of thermal ink-jetting as a method for dosing drugs onto oral films. Methods: A Hewlett-Packard printer cartridge was modified so that aqueous drug solutions replaced the ink. The performance of the printer as a function of print solution viscosity and surface tension was determined; viscosities between 1.1 and 1.5 mm s were found to be optimal, while surface tension did not affect deposition. A calibration curve for salbutamol sulphate was prepared, which demonstrated drug deposition onto an acetate film varied linearly with concentration (r = 0.9992). The printer was then used to deposit salbutamol sulphate onto an oral film made of potato starch. Results: It was found that when doses were deposited in a single pass under the print head, then the measured dose was in good agreement with the theoretical dose. With multiple passes the measured dose was always significantly less than the theoretical dose. It is proposed that the losses arise from erosion of the printed layer by shearing forces during paper handling. The losses were predictable, and the variance in dose deposited was always less than the BP limits for tablet and oral syrup salbutamol sulphate preparations. Conclusions: TIJ printing offers a rapid method for extemporaneous preparation of personalized-dose medicines. [ABSTRACT FROM AUTHOR]

Abstract: We all respond differently to drugs. Personalised medicine aims to improve efficacy and reduce side effects, and efforts are being made to understand the physiological differences that underlie responses to drugs. Genetics, diet and disease state can be key; however, gender also plays an important role in pharmacokinetics, pharmacodynamics and drug toxicity. Differences in metabolism and clearance of drugs as a consequence of distinct hepatic and renal processes in males and females are now much better understood but little is known about gender differences in the gastrointestinal tract. As the recipient of all orally administered medications, differences at this level can have a major impact on drug delivery and bioavailability; yet these continue to be ignored and insufficiently studied in the context of drug disposition. The aim of this review is to highlight the known gender differences in gut physiology. Clinical case studies are presented, where possible, to illustrate the influence of these differences on drug disposition and gaps in current knowledge are highlighted to encourage further research in this area. [Copyright &y& Elsevier]

Currently, pharmaceutical companies are reluctant to introduce pharmacogenomics (PGx) in their practice, since cost–benefit of PGx is obscure and methodology to use PGx in drug development has not been fully established yet. The purpose of this study is to investigate advantages obtained by introducing PGx in clinical trials. Particularly, taking Warfarin as an example, we investigate benefits of Enrichment effect that raises response rate of the drug by PGx. When response rate is raised by only 5%, cost of a clinical trial can be reduced to about 40% of a conventional clinical trial. Furthermore, since period necessary for a trial also can be reduced, development period can be shortened by about 750 days. In summary, PGx enables earlier launch of a drug with less cost, representing benefit to pharmaceutical companies, patients and public as a whole. [ABSTRACT FROM AUTHOR]

[Display omitted] Food-mediated changes to drug absorption, termed the food effect, are hard to predict and can have significant implications for the safety and efficacy of oral drug products in patients. Mimicking the prandial states of the human gastrointestinal tract in preclinical studies is challenging, poorly predictive and can produce difficult to interpret datasets. Machine learning (ML) has emerged from the computer science field and shows promise in interpreting complex datasets present in the pharmaceutical field. A ML-based approach aimed to predict the food effect based on an extensive dataset of over 311 drugs with more than 20 drug physicochemical properties, referred to as features. Machine learning techniques were tested; including logistic regression, support vector machine, k-Nearest neighbours and random forest. First a standard ML pipeline using a 80:20 split for training and testing was tried to predict no food effect, negative food effect and positive food effect, however this lead to specificities of less than 40%. To overcome this, a strategic ML pipeline was devised and three tasks were developed. Random forest achieved the strongest performance overall. High accuracies and sensitivities of 70%, 80% and 70% and specificities of 71%, 76% and 71% were achieved for classifying; (i) no food effect vs food effect, (ii) negative food vs positive food effect and (iii) no food effect vs negative food effect vs positive food effect, respectively. Feature importance using random forest ranked the features by importance for building the predictive tasks. The calculated dose number was the most important feature. Here, ML has provided an effective screening tool for predicting the food effect, with the potential to select lead compounds with no food effect, reduce the number of animal studies, and accelerate oral drug development studies. [ABSTRACT FROM AUTHOR]

[Display omitted] 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. [ABSTRACT FROM AUTHOR]

Dry eye disease is a common ocular disorder that is characterised by tear deficiency or excessive tear evaporation. Current treatment involves the use of eye drops; however, therapeutic efficacy is limited because of poor ocular bioavailability of topically applied formulations. In this study, digital light processing (DLP) 3D printing was employed to develop dexamethasone-loaded punctal plugs. Punctal plugs with different drug loadings were fabricated using polyethylene glycol diacrylate (PEGDA) and polyethylene glycol 400 (PEG 400) to create a semi-interpenetrating network (semi-IPN). Drug-loaded punctal plugs were characterised in terms of physical characteristics (XRD and DSC), potential drug-photopolymer interactions (FTIR), drug release profile, and cytocompatibility. In vitro release kinetics of the punctal plugs were evaluated using an in-house flow rig model that mimics the subconjunctival space. The results showed sustained release of dexamethasone for up to 7 days from punctal plugs made with 20% w/w PEG 400 and 80% w/w PEGDA, while punctal plugs made with 100% PEGDA exhibited prolonged releases for more than 21 days. Herein, our study demonstrates that DLP 3D printing represents a potential manufacturing platform for fabricating personalised drug-loaded punctal plugs with extended release characteristics for ocular administration. [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. [ABSTRACT FROM AUTHOR]

[Display omitted] Counterfeiting of the products for healing is as old as trading, and it is difficult to quantify the magnitude of the problem. It is known that substandard and/or falsified (SF) medicines are a growing global threat to health, and they cause serious social and economic damage. The EU has a strong legal framework for medicines, it is mandatory to meet the requirements of Directive 2011/62/EU. Serialisation prevents SF medicinal products from entering the legal distribution chain. The present study is an extension of the original idea and aims to develop a laser technology-based method to mark an individual traceable code on the surface of the tablet, which technology can also be used for marking personalized medicines. The method is based on the ablation of the upper layer of a double-layer, differently coloured coating. The 2D code should be formed without harming the functional layer, and anyone with a smartphone integrated with a camera should be able to authenticate these drugs with a suitable application. The present findings confirmed that KrF excimer laser and Ti:sapphire femtosecond laser are efficient and reliable for marking. These should be promising candidates for pharmaceutical companies that would like to have additional protection against drug counterfeiters. [ABSTRACT FROM AUTHOR]

The pharmaceutical industry is moving towards the future and is witnessing innovation in drug development through the introduction of personalized medicine technologies. Instead of adapting the dose thata patient needs, they were adapted to the manufacturer's dose. Nowpatient-specific or customized dosing methods and dosing combinations have superior persistence to the standard mass-produced drugs. Printing technology has gained interest during the last few years to manufacture personalized dosage forms. For manufacturing personalized drug products, three-dimensional printing (3DP) has expanded to the pharmaceutical industry. With the approval of the first 3DP product, an unprecedented opportunity for discovering new compounds and technologies has arisen. This article has re-evaluated various printing technology and theirutilization in personalized medicines. Further, we also discussed its history, advantages, challenges and differenttypes of printing technologies with advantages and limitations, particularly in the area of pharmaceutical research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This article identifies the potential sources of inequity in three stages of integrating cystic fibrosis personalized medicines into the Canadian healthcare system and proposes mitigating strategies: (1) clinical research and diagnostic testing; (2) regulatory oversight and market authorization; and (3) implementation into the healthcare system. There is concern that differential access will cast a dark shadow over personalized medicine by stratifying the care that groups of patients will receive—not only based on their genetic profiles, but also on the basis of their socioeconomic status. Furthermore, there is a need to re-evaluate regulatory and market approval mechanisms to accommodate the unique nature of personalized medicines. Physical and financial accessibility ought to be remedied before personalized medicines can be equitably delivered to patients. This article identifies the socio–ethical and legal challenges at each stage and recommends mitigating policy solutions. [ABSTRACT FROM AUTHOR]

Patient responses to doses vary widely, and affording limited doses to such a diverse population will inevitably yield unsatisfactory therapeutic effects and even adverse effects. In Particular, there is an urgent demand for a dynamic dose-control platform for pediatric patients, many of whom require diverse doses and flexible dose adjustments. The aim of this study was to explore the possibility of using a drop-on-powder (DoP) technology-based desktop 3D printer to build a dynamic dose-control platform for theophylline (TP) and metoprolol tartrate (MT). In addition, the impact of drug loading patterns on the accuracy of dose regulation was also assessed. All of the printed tablets exhibited good mechanical properties and satisfactory structural integrity. On printing tablets with target drug doses, the accuracy was in the range of 91.2~108% with a small variation coefficient in the range of 0.5~3.2%. Compared with traditional divided-dose methods, drop-on-powder 3D printing technology exhibited higher accuracy in dose regulation, but had less impact on the in vitro drug release behavior. The results in this work clearly indicate the possibility and ability of DoP technology as a promising method for constructing a dynamic dose-control platform for the fabrication of personalized medicines for pediatric patients. [ABSTRACT FROM AUTHOR]

Active pharmaceutical ingredients are routinely formulated with a range of excipients in the manufacture of drug products. Excipients are considered to be inert components of the formulations, although recent research has contested its inactive behaviour. This study investigated the effect of the excipient polyethylene glycol 400 (PEG 400) on the oral bioavailability and intestinal permeability of cimetidine in male and female human volunteers. Aqueous solutions of cimetidine with pharmaceutically relevant concentrations of PEG 400 at 0% w/v (control), 0.3% w/v, 0.5% w/v, 0.7% w/v and 1.0% w/v were orally administered to both sexes. Urine samples were then collected and assayed for the determination of cimetidine which reflected oral bioavailability. This human study showed that PEG 400 at 0.3% w/v, 0.5% w/v and 0.7% w/v concentrations significantly increased cimetidine bioavailability by 34%, 58% and 41% respectively, although this enhancement was only demonstrated in men and not women (p < 0.05). Ussing chamber transport studies with male human jejunal tissues revealed that cimetidine permeability increased by 26%, 48% and 29% with PEG 400 at 0.3% w/v, 0.5% w/v and 0.7% w/v respectively (p < 0.05). No such enhancement was demonstrated in female tissues (p > 0.05). We have shown that PEG 400 interacts with intestinal P-glycoprotein (P-gp) expression differently in males and females. The mechanistic action of PEG 400 at gut level was further investigated on human jejunal tissues following the pre-treatment of the P-gp inhibitor PSC 833 (valspodar) on the transport of cimetidine. When intestinal P-gp was inhibited, the sex- and dose-dependent modulatory effect of PEG 400 with cimetidine was completely eradicated, thus confirming that PEG 400 has a modulatory – rather than inhibitory – effect on P-gp. In sum, the widely used excipient PEG 400 is not inert at pharmaceutically relevant concentrations and its modulatory effect is demonstrated at a human clinical level. Such pharmacological effects, however, are sex- and dose-dependent via its modulation on intestinal P-gp, as evidenced by the boost in cimetidine bioavailability only in male human volunteers. As such, these findings should be carefully considered towards the co-formulation of PEG 400 with drugs that are P-gp substrates. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Zero-order release formulations are designed to release a drug at a constant rate over a prolonged time, thus reducing systemic side effects and improving patience adherence to the therapy. Such formulations are traditionally complex to manufacture, requiring multiple steps. In this work, fused deposition modeling (FDM) 3D printing was explored to prepare on-demand printlets (3D printed tablets). The design includes a prolonged release core surrounded by an insoluble shell able to provide zero-order release profiles. The effect of drug loading (10, 25, and 40% w/w paracetamol) on the mechanical and physical properties of the hot melt extruded filaments and 3D printed formulations was evaluated. Two different shell 3D designs (6 mm and 8 mm diameter apertures) together with three different core infills (100, 50, and 25%) were prepared. The formulations showed a range of zero-order release profiles spanning 16 to 48 h. The work has shown that with simple formulation design modifications, it is possible to print extended release formulations with tunable, zero-order release kinetics. Moreover, by using different infill percentages, the dose contained in the printlet can be infinitely adjusted, providing an additive manufacturing route for personalizing medicines to a patient. [ABSTRACT FROM AUTHOR]

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. [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. [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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The aim of this mini-review is to highlight the potential applications of next-generation sequencing technology to the field of clinical oncology with respect to genetic diagnosis, cancer classification, predictive biomarkers and personalized medicine., Methods: Scientific databases were searched to collect relative data., Results: Effective systematic analysis of whole-genome sequence and whole-exome sequence of tumors, targeted genome profiling, transcriptome sequencing and tumor-normal comparisons can be performed using NGS in order to diagnosis of several types of cancer., Conclusion: NGS technology can be powerful enough to discover new and infrequent gene alterations, identify hereditary cancer mutation carriers and provide a reliable molecular portrait of wide range of cancers in a quick and cost-effective manner., Competing Interests: Conflict of interest The authors declare that there is no conflict of interests.

Anticancer vaccines train the body's own immune system to recognize and eliminate malignant cells based on differential antigen expression. While conceptually attractive, clinical efficacy is lacking given several key challenges stemming from the similarities between cancerous and healthy tissue. Ideally, an effective vaccine formulation would deliver multiple tumor antigens in a fashion that potently stimulates endogenous immune responses against those antigens. Here, it is reported on the fabrication of a biomimetic, nanoparticulate anticancer vaccine that is capable of delivering autologously derived tumor antigen material together with a highly immunostimulatory adjuvant. The two major components, tumor antigens and adjuvant, are presented concurrently in a fashion that maximizes their ability to promote effective antigen presentation and activation of downstream immune processes. Ultimately, it is demonstrated that the formulation can elicit potent antitumor immune responses in vivo. When combined with additional immunotherapies such as checkpoint blockades, the nanovaccine demonstrates substantial therapeutic effect. Overall, the work represents the rational application of nanotechnology for immunoengineering and can provide a blueprint for the future development of personalized, autologous anticancer vaccines with broad applicability., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)