3D Printing Of Pharmaceuticals Research Articles

Applications and Advancement of 3D Printing in Pharmaceutical Manufacturing and Drug Delivery

Three-dimensional (3D) printing is an innovative additive manufacturing technology that has tremendous potential to revolutionize various aspects of the pharmaceutical industry including drug development, product design, manufacturing and delivery. 3D printing enables precise fabrication of complex drug products with customized compositions and geometries that cannot be produced through conventional processes. It facilitates rapid prototyping thereby accelerating drug development process. 3D printed dosage forms with capability of controlled, delayed and triggered drug release have potential to enhance patient compliance and therapeutic outcomes. Further, 3D printed personalized medications tailored to individual patient needs hold promise to improve medication accessibility and efficacy. Though 3D printing in pharmaceuticals is still in its infancy, ongoing research efforts aim to address key challenges including regulatory compliance, process optimization, material characterization and scale-up. As the technology advances further, 3D printing is expected to significantly transform pharmaceutical manufacturing by making on-demand, decentralized production a reality

3D PRINTING TECHNIQUE: A REVIEW ON THE APPLICATIONS IN PHARMACEUTICAL MANUFACTURING

In the realm of pharmaceutical manufacturing, 3D printing technology stands on the brink of a transformable revolution. This article passionately explores the boundless potential of 3D printing in shaping the future of pharmaceuticals, aiming to inspire researchers. It delves into crucial aspects: an overview of 3D printings in drug development, its advantages in drug production, and the pivotal role of personalized medicine. The article also discusses the creation of patient-specific medical devices, novel drug delivery systems, and the anticipated challenges in adopting 3D printing. Real-world case studies showcase successful applications while addressing the regulatory challenges associated with 3D-printed pharmaceuticals. By bridging existing knowledge gaps, this comprehensive article acts as a guiding light for those dedicated to advancing pharmaceutical research. It empowers researchers with profound insights into this disruptive technology, fostering innovation and collaboration within the community. The untapped potential of 3D printing in pharmaceuticals is vast and promising. Together, researchers can pioneer the future of pharmaceutical manufacturing, benefiting patients globally and propelling scientific advancement. Join us in this exhilarating journey of exploration and discovery as we harness the full capabilities of 3D printing for the betterment of healthcare and the progress of science.

A Comprehensive Review on 3D Printing of Pharmaceuticals

The development of 3D printing technology has caused a paradigm shift in the pharmaceutical industry by making it possible to produce drugs on demand and according to a patient’s specific needs. This review paper aims to examine the developments, difficulties, and potential applications of 3D printing in the pharmaceutical industry. We examine the various methods used, the benefits it provide, the regulatory issues, and possible uses of 3D printing in the pharmaceutical sector. Additionally, we talk about how 3D printing will affect drug research, patient care, and the state of healthcare as a whole.

Microscale 3D printing in pharmaceuticals: From formulation to personalized medicine – An in-depth review

Microscale 3D printing is rapidly transforming the pharmaceutical landscape, offering unprecedented precision and customization in drug formulation and drug delivery systems. This paper explores the current state of the field, highlighting key findings and emerging trends. Microscale 3D printing enables the creation of patient-specific dosages and personalized dosage forms, ushering in an era of precision medicine. Integration with biopharmaceuticals presents novel opportunities in regenerative medicine, with the potential for organ and tissue production. Moreover, the technology holds promise for cost savings and ethical considerations, though challenges in regulation and data protection loom. The future of microscale 3D printing in pharmaceuticals is one of precision, customization and promise, where healthcare is patient-centric and costeffective. This paper provides a comprehensive overview of the subject and underscores the transformative power of this technology.

Optimizing environmental sustainability in pharmaceutical 3D printing through machine learning

3D Printing (3DP) of pharmaceuticals could drastically transform the manufacturing of medicines and facilitate the widespread availability of personalised healthcare. However, with increasing awareness of the environmental damage of manufacturing, 3DP must be eco-friendly, especially when it comes to carbon emissions. This study investigated the environmental effects of pharmaceutical 3DP. Using Design of Experiments (DoE) and Machine Learning (ML), we looked at energy use in pharmaceutical Fused Deposition Modeling (FDM). From 136 experimental runs across four common dosage forms, we identified several key parameters that contributed to energy consumption, and consequently CO2 emission. These parameters, identified by both DoE and ML, were the number of objects printed, build plate temperature, nozzle temperature, and layer height. Our analysis revealed that minimizing trial-and-error by being more efficient in R&D and reducing the build plate temperature can significantly decrease CO2 emissions. Furthermore, we demonstrated that only the ML pipeline could accurately predict CO2 emissions, suggesting ML could be a powerful tool in the development of more sustainable manufacturing processes. The models were validated experimentally on new dosage forms of varying geometric complexities and were found to maintain high accuracy across all three dosage forms. The study underscores the potential of merging sustainability and digitalization in the pharmaceutical sector, aligning with the principles of Industry 5.0. It highlights the comparable learning traits between DoE and ML, indicating a promising pathway for wider adoption of ML in pharmaceutical manufacturing. Through focused efforts to reduce wasteful practices and optimize printing parameters, we can pave the way for a more environmentally sustainable future in pharmaceutical 3DP.

Practical Application of 3D Printing for Pharmaceuticals in Hospitals and Pharmacies.

Three-dimensional (3D) printing is an unrivaled technique that uses computer-aided design and programming to create 3D products by stacking materials on a substrate. Today, 3D printing technology is used in the whole drug development process, from preclinical research to clinical trials to frontline medical treatment. From 2009 to 2020, the number of research articles on 3D printing in healthcare applications surged from around 10 to 2000. Three-dimensional printing technology has been applied to several kinds of drug delivery systems, such as oral controlled release systems, micropills, microchips, implants, microneedles, rapid dissolving tablets, and multiphase release dosage forms. Compared with conventional manufacturing methods of pharmaceutical products, 3D printing has many advantages, including high production rates due to the flexible operating systems and high drug loading with the desired precision and accuracy for potent drugs administered in small doses. The cost of production via 3D printing can be decreased by reducing material wastage, and the process can be adapted to multiple classes of pharmaceutically active ingredients, including those with poor solubility. Although several studies have addressed the benefits of 3D printing technology, hospitals and pharmacies have only implemented this process for a small number of practical applications. This article discusses recent 3D printing applications in hospitals and pharmacies for medicinal preparation. The article also covers the potential future applications of 3D printing in pharmaceuticals.

A case study on decentralized manufacturing of 3D printed medicines

Pharmaceutical 3D printing (3DP) is one of the emerging enabling technologies of personalised medicines as it affords the ability to fabricate highly versatile dosage forms. In the past 2 years, national medicines regulatory authorities have held consultations with external stakeholders to adapt regulatory frameworks to embrace point-of-care manufacturing. The proposed concept of decentralized manufacturing (DM) involves the provision of feedstock intermediates (pharma-inks) prepared by pharmaceutical companies to DM sites for manufacturing into the final medicine. In this study, we examine the feasibility of this model, with respect to both manufacturing and quality control. Efavirenz-loaded granulates (0–35%w/w) were produced by a manufacturing partner and shipped to a 3DP site in a different country. Direct powder extrusion (DPE) 3DP was subsequently used to prepare printlets (3D printed tablets), with mass ranging 266–371 mg. All printlets released more than 80% drug load within the first 60 min of the in vitro drug release test. An in-line near-infrared spectroscopy system was used as a process analytical technology (PAT) to quantify the printlets' drug load. Calibration models were developed using partial least squares regression, which showed excellent linearity (R2 = 0.9833) and accuracy (RMSE = 1.0662). Overall, this work is the first to report the use of an in-line NIR system to perform real-time analysis of printlets prepared using pharma-inks produced by a pharmaceutical company. By demonstrating the feasibility of the proposed distribution model through this proof-of-concept study, this work paves the way for investigation of further PAT tools for quality control in 3DP point-of-care manufacturing.

3D printing of amorphous solid dispersions: A comparison of fused deposition modeling and drop-on-powder printing

Nowadays, a high number of pipeline drugs are poorly soluble and require solubility enhancement by e.g., manufacturing of amorphous solid dispersion. Pharmaceutical 3D printing has great potential in producing amorphous solid oral dosage forms. However, 3D printing techniques differ greatly in terms of processing as well as tablet properties. In this study, an amorphous formulation, which had been printed via Fused Deposition Modeling and drop-on-powder printing, also known as binder jetting, was characterized in terms of solid-state properties and physical stability. Solid state assessment was performed by differential scanning calorimetry, powder X-ray diffraction and polarized microscopy. The supersaturation performance of the amorphous solid dispersion was assessed via non-sink dissolution. We further evaluated both 3D printing techniques regarding their processability as well as tablet uniformity in terms of dimension, mass and content. Challenges and limitations of each 3D printing technique were discussed. Both techniques are feasible for the production of amorphous formulations. Results indicated that Fused Deposition Modeling is better suited for production, as the recrystallization tendency was lower. Still, filament production and printing presented a major challenge. Drop-on-powder printing can be a viable alternative for the production of amorphous tablets, when a formulation is not printable by Fused Deposition Modeling.

Revolutionizing Medical Manufacturing: Unveiling the Diverse Applications of 3D Printing in Pharmaceuticals

Revolutionizing Medical Manufacturing: Unveiling the Diverse Applications of 3D Printing in Pharmaceuticals

A Review: 3D Printing

Abstract: 3D printing or additive manufacturing is a method of creating three dimensional solid matters from a digital file. The design of a 3D printed object is accomplish using additive processes it is also called as RAPID PROTOTYPING. In an additive process an object is manufactured by dozing consecution layers of material as far as the entire object is created.3D concept has the capabilities to furnish benefits for patients, pharmacists and the pharmaceutical industry alike by empower the on-demand design and production of various formulations with individualized dosages, shapes, sizes, drug release and multi-drug combinations. This article criticizing the major benefits for using 3D printing in pharmaceuticals, highlighting the crucial role that healthcare staff play, and will continue to play, in the future implementation of 3D printing into the pharmaceutical sector.

Immediate release 3D printed oral dosage forms: How different polymers have been explored to reach suitable drug release behaviour

Three-dimensional (3D) printing has been gaining attention as a new technological approach to obtain immediate release (IR) dosage forms. The versatility conferred by 3D printing techniques arises from the suitability of using different polymeric materials in the production of solids with different porosities, geometries, sizes, and infill patterns. The appropriate choice of polymer can facilitate in reaching IR specifications and afford other specific properties to 3D printed solid dosage forms. This review aims to provide an overview of the polymers that have been employed in the development of IR 3D printed dosage forms, mainly considering their in vitro drug release behaviour. The physicochemical and mechanical properties of the IR 3D printed dosage forms will also be discussed, together with the manufacturing process strategies. Up to now, methacrylic polymers, cellulosic polymers, vinyl derivatives, glycols and different polymeric blends have been explored to produce IR 3D printed dosage forms. Their effects on drug release profiles are critically discussed here, giving a complete overview to drive formulators towards a rational choice of polymeric material and thus contributing to future studies in 3D printing of pharmaceuticals.

3D printing of pharmaceuticals and the role of pharmacy

Three-dimensional (3D) printing is causing a paradigm shift in pharmaceuticals and clinical pharmacy practice, transitioning away from the traditional mass production of medicines towards tailored drug products that are personalised to each individual. The concept has the potential to provide benefits for patients, pharmacists and the pharmaceutical industry alike by enabling the on-demand design […]

Hot Melt Extrusion and its Application in 3D Printing of Pharmaceuticals.

Hot Melt Extrusion (HME) is a continuous pharmaceutical manufacturing process that has been extensively investigated for solubility improvement and taste masking of active pharmaceutical ingredients. Recently, it is being explored for its application in 3D printing. 3D printing of pharmaceuticals allows flexibility of dosage form design, customization of dosage form for personalized therapy and the possibility of complex designs with the inclusion of multiple actives in a single unit dosage form. Fused Deposition Modeling (FDM) is a 3D printing technique with a variety of applications in pharmaceutical dosage form development. FDM process requires a polymer filament as the starting material that can be obtained by hot melt extrusion. Recent reports suggest enormous applications of a combination of hot melt extrusion and FDM technology in 3D printing of pharmaceuticals and need to be investigated further. This review in detail describes the HME process, along with its application in 3D printing. The review also summarizes the published reports on the application of HME coupled with 3D printing technology in drug delivery.

Evaluation of lactose based 3D powder bed printed pharmaceutical drug product tablets

It is key to understand powder blend characteristics in relation to tablet characteristics when using pharmaceutical 3D printing, in order to obtain 3D powder bed printed tablets that comply with the pharmaceutical specifications. There is limited literature available on excipient selection for 3D printing, even though the only marketed 3D printed drug is prepared with powder bed printing. In this study, the impact of different particle size distributions of lactose-starch base formulations on key critical material attributes such as wettability, consolidation and flowability was studied. It was found that fewer fines in the particle size of the blend is beneficial for a fast penetration time of the ink (liquid) into the powder bed. The impact of varying the print settings or binder type on primary tablet properties such as hardness and dissolution was studied using formulations with Acetaminophen or Diclofenac Sodium. It was found that optimizing the base formulation and print settings have to be in conjunction as they are closely related. This study shows in detail how hydrophilic/hydrophobic API's can be successfully formulated into 3D printed tablets taking into account the formulation considerations as described.

Cellulose and its derivatives for application in 3D printing of pharmaceuticals

Three-dimensional printing (3DP) has emerged as an advanced manufacturing technology capable of producing complex yet precise medicines intended for patient-centric drug therapy. However, printable materials currently available for 3DP are far too limited. The current article covers various cellulose-based polymers as well as their applications, especially in 3DP of oral solid dosage forms. The review focuses on their physicochemical properties, roles, and functions in conventional as well as 3DP dosage forms, and the characteristics of the obtained printed products are discussed. In addition, the challenges and considerations for processing cellulose-based feedstock materials are briefly presented. Cellulose and its derivatives are regarded as suitable polymers with a huge potential for applications in 3DP drug delivery systems. It is therefore essential to better understand cellulose-based printable polymers and their applications in 3DP.

3D printed gummies: Personalized drug dosage in a safe and appealing way.

Obtention of customized dosage forms is one of the main attractions of 3D printing in pharmaceuticals. In this sense, children are one of the groups within the population with a greater need for drug doses adapted to their requirements (age, weight, pathological state…), but most 3D printed oral dosages are solid forms and, therefore, not suitable for them. This work developed patient-tailored medicinal gummies, an alternative oral dosage form with eye-catching appearance and appropriate organoleptic characteristics. Four inks were formulated, characterised and 3D printed by means of syringe-based extrusion mechanism. Different tests were performed to ensure reproducibility of the process and validate work methodology for dosage unit fabrication applying basic manufacturing standards. Rheological test helped in evaluating inks printability. Visual characterization concluded that drugmies, apart from a high fidelity in the 3D model shape reproduction, had a bright and uniformly coloured appearance and a pleasant aroma, which made them highly appetising and attractive. The printed gummy oral dosages complied comfortably with the mass uniformity assay regardless of the formulated ink used or the 3D model selected for printing. Ranitidine hydrochloride individual contents were determined using uv-vis spectrophotometry, showing successful results both in dose accuracy, uniformity of drug content and dissolution.

Benefits and Prerequisites Associated with the Adoption of Oral 3D-Printed Medicines for Pediatric Patients: A Focus Group Study among Healthcare Professionals.

The utilization of three-dimensional (3D) printing technologies as innovative manufacturing methods for drug products has recently gained growing interest. From a technological viewpoint, proof-of-concept on the performance of different printing methods already exist, followed by visions about future applications in hospital or community pharmacies. The main objective of this study was to investigate the perceptions of healthcare professionals in a tertiary university hospital about oral 3D-printed medicines for pediatric patients by means of focus group discussions. In general, the healthcare professionals considered many positive aspects and opportunities in 3D printing of pharmaceuticals. A precise dose as well as personalized doses and dosage forms were some of the advantages mentioned by the participants. Especially in cases of polypharmacy, incorporating several drug substances into one product to produce a polypill, personalized regarding both the combination of drug substances and the doses, would benefit drug treatments of several medical conditions and would improve adherence to medications. In addition to the positive aspects, concerns and prerequisites for the adoption of 3D printing technologies at hospital settings were also expressed. These perspectives are suggested by the authors to be focus points for future research on personalized 3D-printed drug products.

3D DRUG PRINTING- A SWING FROM LABORATORY PRODUCTION TO COMPUTERIZED PRODUCTION

Three-Dimensional (3D) printing is a process where objects are made in successive layers under computer control by fusing or depositing materials. The objects can be of nearly any shape or geometry and come in a computer-aided (CAD) design from 3D model. Since 3D printing began in 1984, it has changed enormously and has been used in a wide range of fields, including medicine and architecture. 3D printing moves rapidly and in future will transform and change the way we live and work from laboratory-based organs to pharmaceutical supplies.
 3D printing in pharmaceuticals has been used to produce many novel dosage forms like microcapsules, complex drug-release profiles, nanosuspensions, and multilayered drug delivery devices. It also offers important advantages from the industrial point of view such as cost-efficiency, higher productivity, democracy-making and enhanced cooperation.
 Keeping in view the recent approval given by USFDA to many drug the focus has now shifted to the personalized medicine as it offers an important benefit to patients who need medications that have narrow therapeutic index or a higher predilection to be influenced by genetic polymorphisms. 3D printer is now seen as a valuable, efficient and economical tool to manufacture individualized medications, tailored to specific patients based on their needs and thereby change the future of pharmacy practice in general and pharmaceutical care in particular.

3D Printing in Pharmaceuticals: Regulatory Perspective.

The last few decades have witnessed enormous advancements in the field of Pharmaceutical drug, design and delivery. One of the recent developments is the advent of 3DP technology. It has earlier been successfully employed in fields like aerospace, architecture, tissue engineering, biomedical research, medical device and others, has recently forayed into the pharmaceutical industry.Commonly understood as an additive manufacturing technology, 3DP aims at delivering customized drug products and is the most acceptable form of"personalized medicine". Data bases and search engines of regulatory agencies like USFDA and EMA have been searched thoroughly for relevant guidelines and approved products. Other portals like PubMed and Google Scholar were also ferreted for any relevant repository of publications are referred to wherever required. So far only one pharmaceutical product has been approved in this category by USFDA and stringent regulatory agencies are working over the drafting of guidelines and technical issues. Major research of this category belongs to the academic domain. It is also implicit to such new technologies that there would be numerous challenges and doubts before these are accepted as safe and efficacious. The situation demands concerted and cautious efforts to bring in foolproof regulatory guidelines which would ultimately lead to the success of this revolutionary technology.

Three dimensional (3D) drug printing: A revolution in pharmaceutical science

Three-dimensional (3D) printing is a manufacturing method in which objects are made by fusing or depositing materials in successive layers laid down under computer control. These objects can be of almost any shape or geometry and are produced from a 3D model as defined in a computer-aided design (CAD). Since the inception of 3D printing in 1984 it has evolved immensely and has been used in many fields including medicine, architecture and more recently in pharmaceutical manufacturing. From lab grown organs to drug delivery devices, 3D printing is advancing rapidly and in future course of time it is going to transform and change the way we live and work. 3D printing in pharmaceuticals has been used to produce many novel dosage forms like microcapsules, Complex Drug-Release Profiles, nanosuspensions, and multilayered drug delivery devices. From industrial point of view it also offers important advantages like, cost-effectiveness, increased productivity, democratization of design and manufacturing, and enhanced collaboration. Keeping in view the recent approval given by USFDA to the first 3D printed antiepileptic drug the focus has now shifted to the personalized medicine as it offers an important benefit to patients who need medications that have narrow therapeutic indices or a higher predilection to be influenced by genetic polymorphisms. 3D printer is now seen as a valuable, efficient and economical tool to manufacture individualized medications, tailored to specific patients based on their needs and thereby change the future of pharmacy practice in general and pharmaceutical care in particular.