Current Pharmaceutical Design - Volume 24, Issue 42, 2018

Background: A recently FDA approved 3D printed drug is paving a path for new pharmaceutical manufacturing era. The 3D printing is a novel approach of producing 3D pharmaceuticals from digital designs, in a layer-by-layer fashion. However, traditional manufacturing of drug products is being carried out from decades with well-established manufacturing processes and with well approved regulatory guidelines but these processes are too obsolete in concern of process aptitude and manufacturing flexibility. On the other hand, 3D printing provides a competitive flexibility in terms of personalized drug dosage forms with complex geometries that will be made on-demand with desired drug release kinetics, hence providing the formulator a substantial provision of improvising the safety and efficacy of the drugs. Furthermore, this novel 3D technology allows tailoring of composite tissue scaffolds and sample models for characterization that closely mimic in-vivo simulations. Nevertheless, certain limitations are there in terms of regulatory aspects hindering the launch of 3DP products in the market. Methods: Exhaustive search were made on Google Scholar and PubMed databases concerning 3-D printing methods, drug delivery applications, and past to present evolution of personalized medicine. Results: Although a high magnitude of progress have been made on 3-D printing techniques in a short span of time, still inkjet, nozzle-based deposition, stereolithography and selective laser sintering techniques are the most popular ones. Their application is adapted in the fabrication of tablets, implants, polypills and nanoparticles. Conclusion: 3D printing is revolutionizing the pharma expectations towards customized medicines but still there is a need to explore the aspects of cost, flexibility and bioequivalence. The present review provides a comprehensive account of various 3D printing technologies and highlights the opportunities and key challenges of 3D printing relevant to pharmaceuticals.

Background: In the last decades, 3D-printing has been investigated and used intensively in the field of tissue engineering, automotive and aerospace. With the first FDA approved printed medicinal product in 2015, the research on 3D-printing for pharmaceutical application has attracted the attention of pharmaceutical scientists. Due to its potential of fabricating complex structures and geometrics, it is a highly promising technology for manufacturing individualized dosage forms. In addition, it enables the fabrication of dosage forms with tailored drug release profiles. Objective: The aim of this review article is to give a comprehensive overview of the used 3D-printing techniques for pharmaceutical applications, including information about the required material, advantages and disadvantages of the respective technique. Methods: For the literature research, relevant keywords were identified and the literature was then thoroughly researched. Conclusion: The current status of 3D-printing as a manufacturing process for pharmaceutical dosage forms was highlighted in this review article. Moreover, this article presents a critical evaluation of 3D-printing to control the dose and drug release of printed dosage forms.

Background: 3D printing (3DP) is an emerging technique for fabrication of a variety of structures and complex geometries using 3D model data. In 1986, Charles Hull introduced stereolithography technique that took advances to beget new methods of 3D printing such as powder bed fusion, fused deposition modeling (FDM), inkjet printing, and contour crafting (CC). Being advantageous in terms of less waste, freedom of design and automation, 3DP has been evolved to minimize incurred cost for bulk production of customized products at the industrial outset. Due to these reasons, 3DP technology has acquired a significant position in pharmaceutical industries. Numerous polymers have been explored for manufacturing of 3DP based drug delivery systems for patient-customized medication with miniaturized dosage forms. Method: Published research articles on 3D printed based drug delivery have been thoroughly studied and the polymers used in those studies are summarized in this article. Results: We have discussed the polymers utilized to fabricate 3DP systems including their processing considerations, and challenges in fabrication of high throughput 3DP based drug delivery systems. Conclusion: Despite several advantages of 3DP in drug delivery, there are still a few issues that need to be addressed such as lower mechanical properties and anisotropic behavior, which are obstacles to scale up the technology. Polymers as a building material certainly plays crucial role in the final property of the dosage form. It is an effort to bring an assemblage of critical aspects for scientists engaged in 3DP technology to create flexible, complex and personalized dosage forms.

Three-dimensional printing (3DP) has a significant impact on organ transplant, cosmetic surgery, surgical planning, prosthetics and other medical fields. Recently, 3 DP attracted the attention as a promising method for the production of small-scale drug production. The knowledge expansion about the population differences in metabolism and genetics grows the need for personalised medicine substantially. In personalised medicine, the patient receives a tailored dose and the release profile is based on his pharmacokinetics data. 3 DP is expected to be one of the leading solutions for the personalisation of the drug dispensing. This technology can fabricate a drug-device with complicated geometries and fillings to obtain the needed drug release profile. The extrusionbased 3 DP is the most explored method for investigating the feasibility of the technology to produce a novel dosage form with properties that are difficult to achieve using the conventional industrial methods. Extrusionbased 3 DP is divided into two techniques, the semi-solid extrusion (SSE) and the fused deposition modeling (FDM). This review aims to explain the extrusion principles behind the two techniques and discuss their capabilities to fabricate novel dosage forms. The advantages and limitations observed through the application of SSE and FDM for fabrication of drug dosage forms were discussed in this review. Further exploration and development are required to implement this technology in the healthcare frontline for more effective and personalised treatment.

Background: Three-dimensional printing (3DP) is a novel technology for fabrication of personalized medicine. As of late, FDA affirmed 3D printed tranquilize item in August 2015, which is characteristic of another section of Pharmaceutical assembling. 3DP incorporates a wide range of assembling procedures, which are altogether founded on computer-aided design (CAD), and controlled deposition of materials (layer-by-layer) to make freestyle geometries. Conventionally, many pharmaceutical processes like compressed tablet have been used from many years for the development of tablet with established regulatory pathways. But this simple process is outdated in terms of process competence and manufacturing flexibility (design space). 3DP is a new technology for the creation of plan, proving to be superior for complex products, customized items and items made on-request. It creates new opportunities for improving efficacy, safety, and convenience of medicines. Method: There are many of the 3D printing technology used for the development of personalized medicine on demand for better treatment like 3D powder direct printing technology, fused-filament 3D printing, 3D extrusion printer, piezoelectric inkjet printer, fused deposition 3D printing, 3D printer, ink-jet printer, micro-drop inkjet 3DP, thermal inkjet printer, multi-nozzle 3D printer, stereolithographic 3D printer. Result: This review highlights features how item and process comprehension can encourage the improvement of a control technique for various 3D printing strategies. Conclusion: It is concluded that the 3D printing technology is a novel potential for manufacturing of personalized dose medicines, due to better patient compliance which can be prepared when needed.

Background: The conventional dosage forms cannot be administered to all patients because of interindividual variability found among people of different race coupled with different metabolism and cultural necessities. Therefore, to address this global issue there is a growing focus on the fabrication of new drug delivery systems customised to individual needs. Medicinal products printed using 3-D technology are transforming the current medicine business to a plausible alternative of conventional medicines. Methods: The PubMed database and Google scholar were browsed by keywords of 3-D printing, drug delivery, and personalised medicine. The data about techniques employed in the manufacturing of 3-D printed medicines and the application of 3-D printing technology in the fabrication of individualised medicine were collected, analysed and discussed. Results: Numerous techniques can fabricate 3-D printed medicines however, printing-based inkjet, nozzle-based deposition and laser-based writing systems are the most popular 3-D printing methods which have been employed successfully in the development of tablets, polypills, implants, solutions, nanoparticles, targeted and topical dug delivery. In addition, the approval of Spritam® containing levetiracetam by FDA as the primary 3-D printed drug product has boosted its importance. However, some drawbacks such as suitability of manufacturing techniques and the available excipients for 3-D printing need to be addressed to ensure simple, feasible, reliable and reproducible 3-D printed fabrication. Conclusion: 3-D printing is a revolutionary in pharmaceutical technology to cater the present and future needs of individualised medicines. Nonetheless, more investigations are required on its manufacturing aspects in terms cost effectiveness, reproducibility and bio-equivalence.

Background: 3D printed pharmaceutical products are revolutionizing the pharmaceutical industry as a prospective mean to achieve a personalized method of treatments acquired to the specially designed need of each patient. It will depend upon age, weight, concomitants, pharmacogenetics and pharmacokinetic profile of the patient and thus transforming the current pharmaceutical market as a potential alternative to conventional medicine. 3D printing technology is getting more consideration in new medicine formulation development as a modern and better alternative to control many challenges associated with conventional medicinal products. There are many advantages of 3D printed medicines which create tremendous opportunities for improving the acceptance, accuracy and effectiveness of these medicines. In 2015, United State Food and Drug Administration has approved the first 3D printed tablet (Spritam®) and had shown the emerging importance of this technology. Methods: This review article summarizes as how in-depth knowledge of drugs and their manufacturing processes can assist to manage different strategies for various 3D printing methods. The principal goal of this review is to provide a brief introduction about the present techniques employed in tech -medicine evolution from conventional to a novel drug delivery system. Results: It is evidenced that through its unparalleled advantages of high-throughput, versatility, automation, precise spatial control and fabrication of hierarchical structures, the implementation of 3D printing for the expansion and delivery of controlled drugs acts as a pivotal role. Conclusion: 3D printing technology has an extraordinary ability to provide elasticity in the manufacturing and designing of composite products that can be utilized in programmable and personalized medicine. Personalized medicine helps in improving drug safety and minimizes side effects such as toxicity to individual human being which is associated with unsuitable drug dose.

Background: 3D printing technology is a new chapter in pharmaceutical manufacturing and has gained vast interest in the recent past as it offers significant advantages over traditional pharmaceutical processes. Advances in technologies can lead to the design of suitable 3D printing device capable of producing formulations with intended drug release. Methods: This review summarizes the applications of 3D printing technology in various drug delivery systems. The applications are well arranged in different sections like uses in personalized drug dosing, complex drugrelease profiles, personalized topical treatment devices, novel dosage forms and drug delivery devices and 3D printed polypills. Results: This niche technology seems to be a transformative tool with more flexibility in pharmaceutical manufacturing. Typically, 3D printing is a layer-by-layer process having the ability to fabricate 3D formulations by depositing the product components by digital control. This additive manufacturing process can provide tailored and individualized dosing for treatment of patients different backgrounds with varied customs and metabolism pattern. In addition, this printing technology has the capacity for dispensing low volumes with accuracy along with accurate spatial control for customized drug delivery. After the FDA approval of first 3D printed tablet Spritam, the 3D printing technology is extensively explored in the arena of drug delivery. Conclusion: There is enormous scope for this promising technology in designing various delivery systems and provides customized patient-compatible formulations with polypills. The future of this technology will rely on its prospective to provide 3D printing systems capable of manufacturing personalized doses. In nutshell, the 3D approach is likely to revolutionize drug delivery systems to a new level, though need time to evolve.

Background: 3D printing/Additive Manufacturing seems a pragmatic approach to realize the quest for a truly customized and personalized drug delivery. 3DP technology, with innovations in pharmaceutical development and an interdisciplinary approach to finding newer Drug Delivery Systems can usher a new era of treatments to various diseases. The true potential of this is yet to be realized, and the US-FDA is focusing on the regulatory science of 3D printed medical devices to help patients access this technology safely and effectively. The approval of the first 3D printed prescription medicine by FDA is a promising step in the translation of more research in this area. Methods: A web-search on PubMed, ScienceDirect, and Nature was performed with the keywords Customized 3D printing and Drug delivery, publications dealing with the aspects of drug delivery using 3D printing for personalized or customized delivery were further considered and analyzed and discussed. Results: We present the advantages offered by 3DP over conventional methods of formulation development and discuss the current state of 3DP in pharmaceutics and how it can be used to develop a truly customized drug delivery system, various 3DP technologies including Stereolithography (SLA), Selective Laser Sintering (SLS), Fused Deposition Modelling (FDM), Pressure Assisted Microsyringe (PAM) that have been used to develop pharmaceutical products have been discussed along with their limitations and also the regulatory considerations to help formulation scientists envisaging research in this area with the necessary information. Conclusion: 3D printing has the potential to fabricate a customized drug delivery system. Presence of many drug formulation and the devices are already in the regulatory approval process indicating its success.

Background: Personalized medicines are becoming more popular as they enable the use of patient’s genomics and hence help in better drug design with fewer side effects. In fact, several doses can be combined into one dosage form which suits the patient’s demography. 3 Dimensional (3D) printing technology for personalized medicine is a modern day treatment method based on genomics of patient. Methods: 3D printing technology uses digitally controlled devices for formulating API and excipients in a layer by layer pattern for developing a suitable personalized drug delivery system as per the need of patient. It includes various techniques like inkjet printing, fused deposition modelling which can further be classified into continuous inkjet system and drop on demand. In order to formulate such dosage forms, scientists have used various polymers to enhance their acceptance as well as therapeutic efficacy. Polymers like polyvinyl alcohol, poly (lactic acid) (PLA), poly (caprolactone) (PCL) etc can be used during manufacturing. Results: Varying number of dosage forms can be produced using 3D printing technology including immediate release tablets, pulsatile release tablets, and transdermal dosage forms etc. The 3D printing technology can be explored successfully to develop personalized medicines which could play a vital role in the treatment of lifethreatening diseases. Particularly, for patients taking multiple medicines, 3D printing method could be explored to design a single dosage in which various drugs can be incorporated. Further 3D printing based personalized drug delivery system could also be investigated in chemotherapy of cancer patients with the added advantage of the reduction in adverse effects. Conclusion: In this article, we have reviewed 3D printing technology and its uses in personalized medicine. Further, we also discussed the different techniques and materials used in drug delivery based on 3D printing along with various applications of the technology.

Background: Pulmonary diseases are the third leading cause of morbidity worldwide, however treatment and diagnosis of these diseases continue to be challenging due to the complex anatomical structure as well as physiological processes in the lungs. Methods: 3D printing is progressively finding new avenues in the medical field and this technology is constantly being used for diseases where diagnosis and treatment heavily rely on the thorough understanding of complex structural-physiology relationships. The structural and functional complexity of the pulmonary system makes it well suited to 3D printing technology. Results: 3D printing can be used to deconstruct the complex anatomy of the lungs and improve our understanding of its physiological mechanisms, cell interactions and pathophysiology of pulmonary diseases. Thus, this technology can be quite helpful in the discovery of novel therapeutic targets, new drugs and devices for the treatment of lung diseases. Conclusion: The intention of this review is to detail our current understanding of the applications of 3D printing in the design and evaluation of inhalable medicines and to provide an overview on its application in the diagnosis and treatment of pulmonary diseases. This review also discusses other technical and regulatory challenges associated with the progression of 3D printing into clinical practice.

Background: 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”. Methods: 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. Results: 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. Conclusion: 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.