Binder jetting 3D printing of challenging medicines: From low dose tablets to hydrophobic molecules.

Increasing access to additive manufacturing technologies utilising easily available desktop devices opened novel ways for formulation of personalized medicines. It is, however, challenging to propose a flexible and robust formulation platform which can be used for fabrication of tailored solid dosage forms composed of APIs with different properties (e.g., hydrophobicity) without extensive optimization. This manuscript presents a strategy for formulation of fast dissolving tablets using binder jetting (BJ) technology. The approach is demonstrated using two model APIs: hydrophilic quinapril hydrochloride (QHCl, logP = 1.4) and hydrophobic clotrimazole (CLO, logP = 5.4). The proposed printing method uses inexpensive, well known, and easily available FDA approved pharmaceutical excipients. The obtained model tablets had uniform content of the drug, excellent mechanical properties, and highly porous structure resulting in short disintegration time and fast dissolution rate. The tablets could be scaled and obtained in predesigned shapes and sizes. The proposed method may find its application in the early stages of drug development where high flexibility of the formulation is required and the amount of available API is limited.

The Impact of EBM-Manufactured Ti6Al4V ELI Alloy Surface Modifications on Cytotoxicity toward Eukaryotic Cells and Microbial Biofilm Formation.

Electron beam melting (EBM) is an additive manufacturing technique, which allows forming customized implants that perfectly fit the loss of the anatomical structure of bone. Implantation efficiency depends not only on the implant's functional or mechanical properties but also on its surface properties, which are of great importance with regard to such biological processes as bone regeneration or microbial contamination. This work presents the impact of surface modifications (mechanical polishing, sandblasting, and acid-polishing) of EBM-produced Ti6Al4V ELI implants on essential biological parameters. These include wettability, cytotoxicity toward fibroblast and osteoblast cell line, and ability to form biofilm by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Obtained results indicated that all prepared surfaces exhibited hydrophilic character and the highest changes of wettability were obtained by chemical modification. All implants displayed no cytotoxicity against osteoblast and fibroblast cell lines regardless of the modification type. In turn, the quantitative microbiological tests and visualization of microbial biofilm by means of electron microscopy showed that type of implant's modification correlated with the species-specific ability of microbes to form biofilm on it. Thus, the results of the presented study confirm the relationship between such technological aspects as surface modification and biological properties. The provided data are useful with regard to applications of the EBM technology and present a significant step towards personalized, customized implantology practice.

Assessment of Mechanical, Chemical, and Biological Properties of Ti-Nb-Zr Alloy for Medical Applications.

The purpose of this work is to obtain comprehensive reference data of the Ti-13Nb-13Zr alloy base material: its microstructure, mechanical, and physicochemical properties. In order to obtain extensive information on the tested materials, a number of examination methods were used, including SEM, XRD, and XPS to determine the phases occurring in the material, while mechanical properties were verified with static tensile, compression, and bending tests. Moreover, the alloy's corrosion resistance in Ringer's solution and the cytotoxicity were investigated using the MTT test. Studies have shown that this alloy has the structure α', α, and ß phases, indicating that parts of the ß phase transformed to α', which was confirmed by mechanical properties and the shape of fractures. Due to the good mechanical properties (E = 84.1 GPa), high corrosion resistance, as well as the lack of cytotoxicity on MC3T3 and NHDF cells, this alloy meets the requirements for medical implant materials. Ti-13Nb-13Zr alloy can be successfully used in implants, including bone tissue engineering products and dental applications.