Fabrication of timed-release indomethacin core-shell tablets for chronotherapeutic drug delivery using dual nozzle fused deposition modeling (FDM) 3D printing.

In the present study, timed-release indomethacin tablets, releasing drug after predetermined lag times, were developed for the effective treatment of early morning stiffness in rheumatoid arthritis using two-nozzle fused deposition modeling (FDM) 3D printing with a Bowden extruder. The developed core-shell tablets consisted of a drug-containing core and release-regulating shell with different designed thicknesses (i.e., 0.4 mm, 0.6 mm, 0.8 mm). The filaments to fabricate cores and shells were prepared using hot-melt extrusion (HME), and different filament compositions were formulated for core tablets and screened for rapid release and printability. Eventually, the HPMCAS-based formulation comprised a core tablet enclosed by a shell of Affinisol™ 15LV, a swellable polymer. During 3D printing, one nozzle was dedicated to printing core tablets loaded with indomethacin, and the other nozzle was dedicated to printing shells, making a whole structure produced at once without inconvenient filament change and nozzle cleanout. The mechanical properties of filaments were compared using a texture analyzer. The core-shell tablets were characterized for dissolution profiles and physical attributes (e.g., dimension, friability, hardness). SEM image indicated a smooth and complete surface of the core-shell tablets. The tablets showed 4-8 h of lag depending on the shell thicknesses and released most of the drugs in 3 h, regardless of the shell thicknesses. The core-shell tablets showed high reproducibility but exhibited low dimensional accuracy in the shell thickness. This study explored the suitability of using two-nozzle FDM 3D printing with Bowden extrusion for producing personalized chronotherapeutic core-shell tablets and discussed possible challenges that needed to be considered for a successful printing process using this technology.

The Finite Element Analysis Research on Microneedle Design Strategy and Transdermal Drug Delivery System.

Microneedles (MNs) as a novel transdermal drug delivery system have shown great potential for therapeutic and disease diagnosis applications by continually providing minimally invasive, portable, cost-effective, high bioavailability, and easy-to-use tools compared to traditional parenteral administrations. However, microneedle transdermal drug delivery is still in its infancy. Many research studies need further in-depth exploration, such as safety, structural characteristics, and drug loading performance evaluation. Finite element analysis (FEA) uses mathematical approximations to simulate real physical systems (geometry and load conditions). It can simplify complex engineering problems to guide the precise preparation and potential industrialization of microneedles, which has attracted extensive attention. This article introduces FEA research for microneedle transdermal drug delivery systems, focusing on microneedle design strategy, skin mechanics models, skin permeability, and the FEA research on drug delivery by MNs.

3D printing in personalized drug delivery: An overview of hot-melt extrusion-based fused deposition modeling.

Advancements in pharmaceutical technologies have led to the personalization of therapies over the last decade. Three-dimensional printing (3DP) is an emerging technique in the manufacturing of pharmaceutical dosage forms because of its potential to create complex and customized dosage forms according to the patient's needs. Among the various 3DP techniques based on different functioning mechanisms, fused deposition modeling (FDM) 3D printing is a versatile and widely used method with advantages such as precision of quantity and the ability to incorporate different fill densities. This method is also economical and easily produces complex designs. Hot-melt extrusion (HME) is an established technique in pharmaceutical manufacturing that is utilized in the development of filaments which are used as "ink roll" or feedstock material in FDM 3D printing. This review discusses the various stages involved in FDM 3D printing, including feedstock filament preparation using HME, digital dosage form designs, filament characterization, and various novel applications, and future perspectives.

3D Printing in Personalized Drug Delivery.

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.