3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics.

Fused-filament 3D printing of drug products: Microstructure analysis and drug release characteristics of PVA-based caplets

In recent years, the interest in 3D printing of medicines has increased due to many advantages of this technology, such as flexibility of the dose and dosage form of the printed product. Fused deposition modeling (FDM) is one of the most popular 3D printing technologies in the pharmaceutical field, due to its low cost and simplicity. The subject of this review is the potential use of natural products as biodegradable and biocompatible materials with good safety profiles in FDM 3D printing of pharmaceuticals. Natural products such as alginate, chitosan and starch have already been employed as excipients in FDM 3D printed pharmaceutical dosage forms, while others like shellac and zein show the potential, but haven't yet been part of 3D printed pharmaceutical formulations. These excipients have different roles in the formulation of filaments for FDM 3D printing, for example as fillers, matrix carriers or drug-release modifiers. In addition, the possibility of incorporating active pharmaceutical ingredients of natural origin in filaments for FDM 3D printing was reviewed. High printing temperatures limit the use of natural products in FDM 3D printing. However, adequate selection of thermoplastic material and printing parameters can widen the use of natural products in FDM 3D printing of pharmaceutical dosage forms.

The aim of the present work was to produce 3D-printed oral dosage forms with a sufficient drug dose displaying various release profiles. Hot-melt extrusion was utilized to produce drug-loaded feedstock material that was subsequently 3D-printed into 6, 8, and 10 × 2.5 mm tablets with 15% and 90% infill levels. The prepared formulations contained 30% (w/w) isoniazid in combination with one or multiple pharmaceutical polymers possessing suitable properties for oral drug delivery. Thirteen formulations were successfully hot-melt extruded of which eight had properties suitable for fused deposition modeling 3D printing. Formulations containing HPC were found to be superior regarding printability in this study. Filaments with a breaking distance below 1.5 mm were observed to be too brittle to be fed into the printer. In addition, filaments with high moisture uptake at high relative humidity generally failed to be printable. Different release profiles for the 3D-printed tablets were obtained as a result of using different polymers in the printed formulations. For 8 mm tablets printed with 90% infill, 80% isoniazid release was observed between 40 and 852 min. Drug release characteristics could further be altered by changing the infill or the size of the printed tablets allowing personalization of the tablets. This study presents novel formulations containing isoniazid for prevention of latent tuberculosis and investigates 3D printing technology for personalized production of oral solid dosage forms enabling adjustable dose and drug release properties.

The application of three-dimensional (3D) printing in medicine has increased rapidly in the last few years. Various new commercial 3D printers and 3D bioprinters are introduced into the current market. 3D printing scientific community has witnessed a rapid growth in the application of 3D printing for various medical needs. There has been a research advancement in 4D printing with a widened scope of 3D bioprinting. The growing demand for 3D printing and its use for commercial and industrial purposes in medical technology have facilitated the need for introduction of new international standards and regulations. The need for organ replacement has generated curiosity and competition among researchers to race for organ 3D printing, which can be identified with increased publications and patents that are filed in recent years. Hence, there is a need to update the readers with the latest information. The second edition of this chapter updates the contents of first section to fourth section with current information and some modified pictorial representations. New section describes the relevance of the new chapters added to this edition and updates the readers with insights on advancement of 3D printing in the last decade. Briefly, this chapter introduces the reader with a brief history of 3D printing in medical technology, components of 3D printing, 3D bioprinting, organ 3D bioprinting, advantages of 3D printing with current challenges and commercially available 3D printers in the current market. New sections introduced in this edition detail about the ASTM and ISO standards that are used for 3D printing in medicine, the regulatory framework with current challenges, ethical and social concerns with the current 3D printing scientific community, and the importance of intellectual property in safeguarding the interests of the innovators.

The aim of the study was to investigate core–shell pulsatile tablets by combining the advantages of FDM 3D printing and traditional pharmaceutical technology, which are suitable for a patient’s individual medication and chronopathology. The tablets were designed and prepared with the commercial verapamil hydrochloride tablets as core inside and the fused deposition modelling (FDM) 3D-printed shell outside. Filaments composed of hydroxypropylmethyl cellulose (HPMC) and polyethylenglycol (PEG) 400 were prepared by hot melt extrusion (HME) and used for fabrication of the shell. Seven types of printed shells were designed for the tablets by adjusting the filament composition, geometric structure and thickness of the shell. A series of evaluations were then performed on the 3D-printed core–shell tablets, including the morphology, weight, hardness, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), in vitro drug release and CT imaging. The results showed that the tablets prepared by FDM 3D printing appeared intact without any defects. All the excipients of the tablet shells were thermally stable during the extruding and printing process. The weight, hardness and in vitro drug release of the tablets were affected by the filament composition, geometric structure and thickness of the shell. The pulsatile tablets achieved personalized lag time ranging from 4 h to 8 h in the drug release test in phosphate-buffered solution (pH 6.8). Therefore, the 3D-printed core–shell pulsatile tablets in this study presented good potential in personalized administration, thereby improving the therapeutic effects of the drug for circadian rhythm disease.

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.

BackgroundDespite regulatory advances, lack of age-appropriate formulations (AAFs) remains a challenge in paediatric practice. 3D-printing of oral dosage forms (ODFs) offers potential for AAFs for children. Optimising drug release from...

An Organic Acid-Induced Sigmoidal Release System for Oral Controlled-Release Preparations. 2. Permeability Enhancement of Eudragit RS Coating Led by the Physicochemical Interactions with Organic Acid

Medical three-dimensional (3D) printing is playing an increasingly important role in clinical practice. The use of 3D printed models in patient care offers a wide range of possibilities in terms of personalized medicine, training and education of medical professionals, and communication with patients. DICOM files from imaging modalities such as CT and MRI provide the basis for the majority of the 3D models in medicine. The image acquisition, processing, and interpretation of these lies within the responsibility of radiology, which can therefore play a key role in the application and further development of 3D printing.The purpose of this review article is to provide an overview of the principles of 3D printing in medicine and summarize its most important clinical applications. It highlights the role of radiology as central to developing and administering 3D models in everyday clinical practice.This is a narrative review article on medical 3D printing that incorporates expert opinions based on the current literature and practices from our own medical centers.While the use of 3D printing is becoming increasingly established in many medical specialties in Germany and is finding its way into everyday clinical practice, centralized "3D printing labs" are a rarity in Germany but can be found internationally. These labs are usually managed by radiology departments, as radiology is a connecting discipline that - thanks to the imaging technology used to produce data for 3D printing - can play a leading role in the application of medical 3D printing. Copying this approach should be discussed in Germany in order to efficiently use the necessary resources and promote research and development in the future. · 3D printing in medicine is a rapidly growing field.. · Image acquisition and processing provides an important basis for high-quality 3D models.. · Radiology, as the specialist discipline responsible for imaging, has a crucial role to play.. · Radiology should play a leading role in the introduction of 3D printing in everyday clinical practice. . · Streckenbach A, Schubert N, Streckenbach F et al. Current State and Outlook in Medical 3 D Printing and the Role of Radiology. Fortschr Röntgenstr 2024; DOI 10.1055/a-2436-7185.

An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing

The purpose of this study was to investigate the impact of the drug loading method on drug release from 3D-printed tablets. Filaments comprising a poorly water-soluble model drug, indomethacin (IND), and a polymer, polyvinyl alcohol (PVA), were prepared by hot-melt extrusion (HME) and compared with IND-loaded filaments prepared with an impregnation (IMP) process. The 3D-printed tablets were fabricated using a fused deposition modeling 3D printer. The filaments and 3D printed tablets were evaluated for their physicochemical properties, swelling and matrix erosion behaviors, drug content, and drug release. Physicochemical investigations revealed no drug–excipient interaction or degradation. IND-loaded PVA filaments produced by IMP had a low drug content and a rapid drug release. Filaments produced by HME with a lower drug content released the drug faster than those with a higher drug content. The drug content and drug release of 3D-printed tablets containing IND were similar to those of the filament results. Particularly, drug release was faster in 3D-printed tablets produced with filaments with lower drug content (both by IMP and HME). The drug release of 3D-printed tablets produced from HME filaments with higher drug content was extended to 24 h due to a swelling-erosion process. This study confirmed that the drug loading method has a substantial influence on drug content, which in turn has a significant effect on drug release. The results suggest that increasing the drug content in filaments might delay drug release from 3D-printed tablets, which may be used for developing dosage forms suited for personalized medicine.

Hot-melt extrusion (HME) and subsequent FDM 3D printing offer great potential opportunities in the formulation development and production of customized oral dosage forms with poorly soluble drugs. However, thermal stress within these processes can be challenging for thermo-sensitive drugs. In this work, three different formulations were prepared to investigate the degradation and the solid state of the thermo-sensitive and poorly soluble drug escitalopram oxalate (ESC-OX) during the two heat-intensive processes HME and FDM 3D printing. For this purpose, hydroxypropyl methyl cellulose (HPMC) and basic butylated methacrylate copolymer (bPMMA) were chosen as polymers. DSC and XRD measurements revealed that ESC-OX is amorphous in the HPMC based formulations in both, extrudates and 3D printed tablets. In contrast, in-situ amorphization of the drug from crystalline state in bPMMA filaments was observed during FDM 3D printing. With regard to the content, it was found that degradation of ESC-OX in extrudates with bPMMA could be avoided and in 3D printed tablets almost fully reduced. Furthermore, a possible conversion into the R-enantiomer in the formulation with bPMMA could be excluded using a chiral column. Compared to the commercial product Cipralex®, drug release from extrudates and tablets with bPMMA was slower but still qualified as immediate drug release.

3D Printing is the trending technology in this generation and its usage is increasing day-by-day because it reduces cost of production. FDM (Fused Deposition Modeling) is one type of 3D printing which uses plastics in the form of wire like filament by an extruder for making 3D prints. But, by installing a pellet extruder instead of filament extruder reduces cost of printing process that is 1 kg of PLA pellets cost around 4€ while 1 kg of PLA filament cost around 22€; also, can print wide ranges of materials, increase in speed of prints, chance of recyclability when compared to filament extruder. Whole purpose of this paper is to provide information about installation of a miniature pellet extruder to a 3D printer especially in FDM 3D PRINTERS instead of filament extruder. Most of the FDM 3D printers use plastics in the form of wire like filament for making 3D prints. This paper provides in detail information about FDM and its types, difference between pellet extruder and filament extruder, their advantages and disadvantages, information about some pellet extruders and type of FDM printers they are suitable for. Knowledge from this study will help to choose between pellet extruder and filament extruder which fulfils requirement and which types of pellet extruder have to install to 3D printer depending on its type and requirement.

Chapter 1 - 3D Printing in Medicine: Current Challenges and Potential Applications

Gastro-retentive drug delivery systems (GRDDS) have been used to improve the therapeutic efficacy of drugs with narrow absorption windows, unstable in alkaline pH, soluble in acidic conditions, and active locally in the stomach. This study aimed to produce a novel floating three-dimensional (3D)-printed device (F3D) from polylactic acid filaments using a fused deposition modeling 3D printer. There were two parts of F3D: a cap with an air chamber for floating property and a body with 6 channels for controlled release. The device was designed to have adjustable channels for the releasing control and gastric retention of Bromhexine, carvedilol, and theophylline. The releasing channels could be adjusted by rotating the base to open or close the number of releasing channels as 3 levels (2, 4, and 6 channels). Morphology, weight variation, ex vivo floating time, and drug release characteristics were examined. The F3D had a smooth texture with a narrow SD value of weight variation and actual size, suggesting that the F3D had high accuracy and consistent fabrication using 3D printing technology. All tablets incorporated F3D was able to float for at least 24 h. Decreasing the number of channels on the devices led to the sustained release of drugs following 2> 4> 6 channels. Hence, F3D could be useful in controlling drug release for various commercial tablets. Keywords: 3D-printed device, Floating device, Fused deposition modeling, Gastroretentive drug delivery systems, controlled release dosage form