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[Display omitted] Drug delivery systems capable of being retained within hollow organs allow the entire drug dose to be delivered locally to the disease site or to absorption windows for improved systemic bioavailability. A novel Organ-Retentive Osmotically Driven System (ORODS) was here proposed, obtained by assembling drug-containing units having prolonged release kinetics with osmotic units used as increasing volume compartments. Particularly, prototypes having H-shape design were conceived, manufactured and evaluated. Such devices were assembled by manually inserting a tube made of regenerated cellulose (osmotic unit) into the holes of two perforated hydrophilic tableted matrices containing paracetamol as a tracer drug. The osmotic unit was obtained by folding and gluing a plain regenerated cellulose membrane and loading sodium chloride inside. When immersed in aqueous fluids, this compartment expanded to approximately 80% of its maximum volume within 30 min of testing, and a plateau was maintained for about 6 h. Subsequently, it slowly shrank to approximately 20% of the maximum volume in 24 h, which would allow for physiological emptying of the device from hollow organs. While expanding, the osmotic unit acquired stiffness. Drug release from H-shaped ORODSs conveyed in hard-gelatin capsules was shown to be prolonged for more than 24 h. [ABSTRACT FROM AUTHOR]

The pulsatile-release Chronotopic™ system was conceived of as a drug-containing core surrounded by a coat made of swellable/soluble hydrophilic polymers, the latter being able to provide a programmable lag phase prior to drug liberation. This system was also proposed in a colon-targeting configuration, entailing a gastroresistant film to prevent early interaction of the inner coat with gastric fluids and enabling the attainment of a lag phase matching the small intestinal transit time. Over the years, various multiple-step manufacturing processes have been tested for the fabrication of the Chronotopic™ system in both its configurations. This work focused on the evaluation of 3D printing by fused deposition modeling in view of its potential towards product personalization, on demand one-step manufacturing and efficient scale down of batches. The feasibility of each part of the Chronotopic™ system was independently investigated starting from in-house made filaments, characterizing the resulting specimens for physico-technological and performance characteristics. The printing parameters identified as suitable during the set-up phase were then used to fabricate prototypes either in a single step for the pulsatile configuration or following two different fabrication approaches for the colon-targeting one. [ABSTRACT FROM AUTHOR]

By 3-dimensional (3D) printing, solid objects of any shape are fabricated through layer-by-layer addition of materials based on a digital model. At present, such a technique is broadly exploited in many industrial fields because of major advantages in terms of reduced times and costs of development and production. In the biomedical and pharmaceutical domains, the interest in 3D printing is growing in step with the needs of personalized medicine. Printed scaffolds and prostheses have partly replaced medical devices produced by more established techniques, and more recently, 3D printing has been proposed for the manufacturing of drug products. Notably, the availability of patient-tailored pharmaceuticals would be of utmost importance for children, elderly subjects, poor and high metabolizers, and individuals undergoing multiple drug treatments. 3D printing encompasses a range of differing techniques, each involving advantages and open issues. Particularly, solidification of powder, extrusion, and stereolithography have been applied to the manufacturing of drug products. The main challenge to their exploitation for personalized pharmacologic therapy is likely to be related to the regulatory issues involved and to implementation of production models that may allow to efficiently turn the therapeutic needs of individual patients into small batches of appropriate drug products meeting preset quality requirements. [ABSTRACT FROM AUTHOR]

Fused deposition modeling (FDM) is a 3D printing technique based on the deposition of successive layers of thermoplastic materials following their softening/melting. Such a technique holds huge potential for the manufacturing of pharmaceutical products and is currently under extensive investigation. Challenges in this field are mainly related to the paucity of adequate filaments composed of pharmaceutical grade materials, which are needed for feeding the FDM equipment. Accordingly, a number of polymers of common use in pharmaceutical formulation were evaluated as starting materials for fabrication via hot melt extrusion of filaments suitable for FDM processes. By using a twin-screw extruder, filaments based on insoluble (ethylcellulose, Eudragit ® RL), promptly soluble (polyethylene oxide, Kollicoat ® IR), enteric soluble (Eudragit ® L, hydroxypropyl methylcellulose acetate succinate) and swellable/erodible (hydrophilic cellulose derivatives, polyvinyl alcohol, Soluplus ® ) polymers were successfully produced, and the possibility of employing them for printing 600 μm thick disks was demonstrated. The behavior of disks as barriers when in contact with aqueous fluids was shown consistent with the functional application of the relevant polymeric components. The produced filaments were thus considered potentially suitable for printing capsules and coating layers for immediate or modified release, and, when loaded with active ingredients, any type of dosage forms. [ABSTRACT FROM AUTHOR]

[Display omitted] Shape memory materials (SMMs), including alloys and polymers, can be programmed into a temporary configuration and then recover the original shape in which they were processed in response to a triggering external stimulus (e.g. change in temperature or pH, contact with water). For this behavior, SMMs are currently raising a lot of attention in the pharmaceutical field where they could bring about important innovations in the current treatments. 4D printing involves processing of SMMs by 3D printing, thus adding shape evolution over time to the already numerous customization possibilities of this new manufacturing technology. SMM-based drug delivery systems (DDSs) proposed in the scientific literature were here reviewed and classified according to the target pursued through the shape recovery process. Administration route, therapeutic goal, temporary and original shape, triggering stimulus, main innovation features and possible room for improvement of the DDSs were especially highlighted. [ABSTRACT FROM AUTHOR]

Feasibility of fused deposition modeling in 3D printing of hollow systems intended to convey different formulations for oral administration has recently been investigated. A major advantage of such printed devices is represented by the possibility of separately undertaking the development of the inner core from that of the outer shell, which could also act as a release-controlling barrier. Systems either composed of parts to be filled and assembled after fabrication or fabricated and filled in a single manufacturing process represent the main focus of this review. Devices having relatively simple (e.g. single-compartment capsule-like) configuration were first proposed followed by systems entailing multiple inner compartments. The latter were meant to be filled with different formulations, left empty for ensuring floatation or achieve combined release kinetics. For each of the reviewed systems, design, formulation approaches, manufacturing as well as release performance obtained were critically described. Versatility of FDM, especially in terms of geometric freedom provided, was highlighted together with some limitations that still need to be addressed, as expected for a newly-adopted fabrication technique that holds potential for being implemented in the pharmaceutical field. [ABSTRACT FROM AUTHOR]

Fused deposition modeling 3D printing is currently one of the hot topics in pharmaceutics and has shown a 2000% increase in the number of research articles published in the last 5 years. In the prospect of a new era of fused deposition modeling focused on the industrial development of this technique applied to the fabrication of personalized medicines, a conceptual map to move through the evolution of the design of the printed dosage forms/drug delivery systems was conceived and mainly discussed by means of graphical tools. [ABSTRACT FROM AUTHOR]

Dietary supplement companies have recently started to focus on the personalization of products and the improvement of the relevant performance. In this respect, a versatile, easy-to-handle capsular delivery platform with customizable content and release kinetics was here proposed and evaluated after filling with caffeine as a model dietary ingredient. In particular, capsular devices comprising 1 to 3 independent inner compartments were attained by Lego-inspired assembly of matching modular units with different wall compositions, manufactured by injection molding and fused deposition modeling 3D printing. Accordingly, one-, two- and three-pulse release profiles of the dietary ingredient were obtained from differently assembled devices following the breakup of the compartments occurring promptly (immediate-release), on pH change (delayed-release) or after tunable lag times (pulsatile-release). The latter release mode would enable the onset of the stimulating effect of caffeine at different times of the day after a single administration when convenient. The performance of each individual compartment only depended on the composition (i.e., promptly soluble, swellable/soluble or enteric soluble polymers) and thickness of its own wall, while it was not affected by the composition and number of joined modular units. Moreover, the delivery platform was extended to include an external gastroresistant shell enclosing previously assembled devices. [ABSTRACT FROM AUTHOR]

3D printing, and particularly fused deposition modeling (FDM), has rapidly brought the possibility of personalizing drug therapies to the forefront of pharmaceutical research and media attention. Applications for this technology, described in published articles, are expected to grow significantly in 2020. Where are we on this path, and what needs to be done to develop a FDM 2.0 process and make personalized medicines available to patients? Based on literature analysis, this manuscript aims to answer these questions and highlight the critical technical aspects of FDM as an emerging technology for manufacturing safe, high-quality personalized oral drug products. In this collaborative paper, experts from different fields contribute strategies for ensuring the quality of starting materials and discuss the design phase, printer hardware and software, the process, the environment and the resulting products, from the perspectives of both patients and operators. [ABSTRACT FROM AUTHOR]