Extrusion-based 3D printing technology is a relatively new technique that has a potential for fabricating pharmaceutical products in various dosage forms. It offers many advantages over conventional manufacturing methods, including more accurate drug dosing, which is especially important for the drugs that require exact tailoring (e.g., narrow therapeutic index drugs). In this work, we have successfully fabricated phenytoin-loaded orodispersible films (ODFs) through a syringe extrusion 3D printing technique. Two different grades of hydroxypropyl methylcellulose (HPMC E5 and HPMC E15) were used as the film-forming polymers, and glycerin and propylene glycol were used as plasticizers. The 3D-printed ODFs were physicochemically characterized and evaluated for their mechanical properties and in vitro disintegration time. Then, the optimum printed ODFs showing good mechanical properties and the fastest disintegration time were selected to evaluate their drug content and dissolution profiles. The results showed that phenytoin-loaded E15 ODFs demonstrated superior properties when compared to E5 films. It demonstrated a fast disintegration time in less than 5 s and rapidly dissolved and reached up to 80% of drug release within 10 min. In addition, it also exhibited drug content uniformity within United States Pharmacopeia (USP) acceptable range and exhibited good mechanical properties and flexibility with low puncture strength, low Young’s modulus and high elongation, which allows ease of handling and application. Furthermore, the HPMC E15 printing dispersions with suitable concentrations at 10% w/v exhibited a non-Newtonian (shear-thinning) pseudoplastic behavior along with good extrudability characteristics through the extrusion nozzle. Thus, HPMC E15 can be applied as a 3D printing polymer for a syringe extrusion 3D printer.

The application of hydrophilic polymers in designing and three-dimensional (3D) printing of pharmaceutical products in various dosage forms has recently been paid much attention. Use of hydrophilic polymers and syringe extrusion 3D printing technology in the fabrication of orodispersible films (ODFs) might hold great potential in rapid drug delivery, personalized medicine, and manufacturing time savings. In this study, the feasibility of 3D-printed ODFs fabrication through a syringe extrusion 3D printing technique and using five different hydrophilic polymers (e.g., hydroxypropyl methylcellulose E15, hydroxypropyl methylcellulose E50, high methoxyl pectin, sodium carboxymethylcellulose, and hydroxyethylcellulose) as film-forming polymers and printing materials has been investigated. Rheology properties and printability of printing gels and physicochemical and mechanical properties of 3D-printed ODFs were evaluated. Amongst the investigated hydrophilic polymers, sodium carboxymethylcellulose at a concentration of 5% w/v (SCMC-5) showed promising results with a good printing resolution and accurate dimensions of the 3D-printed ODFs. In addition, SCMC-5 3D-printed ODFs exhibited the fastest disintegration time within 3 s due to high wettability, roughness and porosity on the surface. However, the results of the mechanical properties study showed that SCMC-5 3D printed ODFs were rigid and brittle, thus requiring special packaging to prevent them from any damage before practical use.

Three-dimensional (3D) printing can be used to fabricate custom microneedle (MN) patches instead of the conventional method. In this work, 3D-printed MN patches were utilized to fabricate a MN mold, and the mold was used to prepare dissolving MNs for topical lidocaine HCl (L) delivery through the skin. Topical creams usually take 1–2 h to induce an anesthetic effect, so the delivery of lidocaine HCl from dissolving MNs can allow for a therapeutic effect to be reached faster than with a topical cream. The dissolving-MN-patch-incorporated lidocaine HCl was constructed from hydroxypropyl methylcellulose (HPMC; H) and polyvinyl pyrrolidone (PVP K90; P) using centrifugation. Additionally, the morphology, mechanical property, skin insertion, dissolving behavior, drug-loading content, drug release of MNs and the chemical interactions among the compositions were also examined. H5₁P₂-L, H50₁P₂-L, and H90₁P₂-L showed an acceptable needle appearance without bent tips or a broken structure, and they had a low % height change (80%). These three formulations exhibited a drug-loading content approaching 100%. Importantly, the composition-dependent dissolving abilities of MNs were revealed. Containing the lowest amount of HPMC in its formulation, H90₁P₂-L showed the fastest dissolving ability, which was related to the high amount of lidocaine HCl released through the skin. Moreover, the results of an FTIR analysis showed no chemical interactions among the two polymers and lidocaine HCl. As a result, HPMC/PVP K90 dissolving microneedles can be used to deliver lidocaine HCl through the skin, resulting in a faster onset of anesthetic action.

Silicon photonic devices with either silicon or silicon nitride waveguides have increasingly been used in many applications besides communications, especially as sensors in label-free biosensing, where guided light signals are affected by biorecognition molecules immobilized on the surface. The coating of protein (i.e., bioreceptors) by biochemical process on the waveguide surface is a crucial step in creating a functionalized device that can be used for biosensing. As a conventional method that uses 3-aminopropryltriethoxysilane (APTES) and glutaraldehyde (GA), the APTES-GA method has the limitation of using a GA crosslink, of which the two functional groups can bind to nonspecific proteins, causing irregular binding. In this study, we proposed a new coating technique to avoid such problem by applying APTES silanization with 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide (EDC)-N-hydroxysuccinimide (NHS) protein crosslink, denoted by the APTES-(EDC/NHS) method. The EDC/NHS reaction was shown to be able to immobilize protein in ordered orientation due to consistent arrangement between a carboxylic group of protein molecules and an amine group of covalent-linked APTES on surface. By applying APTES silanization, we circumvented the use of hazardous cleaning agent in the conventional EDC/NHS technique. Several surface characterization techniques were carried out to assess and compare the two biocoating techniques, including scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), spectroscopic ellipsometry (SE), and atomic force microscopy (AFM). On silicon, the results of antihuman TNF-alpha antibody coating showed that the proposed APTES-(EDC/NHS) technique has better repeatability in terms of less roughness of the coated protein at 1.5 nm compared with 6.3 nm, due to the ordered arrangement of coated antibody molecules. On a silicon nitride waveguide device, the proposed APTES-(EDC/NHS) technique exhibits dense antibody immobilization on a waveguide in SEM images due to stable amide bond formation via EDC/NHS crosslink mechanism. The specificity of the immobilized antibodies was confirmed by enzyme-linked immunosorbent assays (ELISA), with an average optical density at 450 nm of 0.175 ± 0.01 compared with 0.064 ± 0.009 of negative control. The proposed technique also reduced the overall process time since proteins are crosslinked to the silanized waveguide surface in a single step.

Tissue engineering technology has been advanced and applied to various applications in the past few years. The presence of a bioreactor is one key factor to the successful development of advanced tissue engineering products. In this work, we developed a programmable bioreactor with a controlling program that allowed each component to be automatically operated. Moreover, we developed a new pH sensor for non-contact and real-time pH monitoring. We demonstrated that the prototype bioreactor could facilitate automatic cell culture of L929 cells. It showed that the cell viability was greater than 80% and cell proliferation was enhanced compared to that of the control obtained by a conventional cell culture procedure. This result suggests the possibility of a system that could be potentially useful for medical and industrial applications, including cultured meat, drug testing, etc.

Depression is a mental illness causing a continuous negative feeling and loss of interest and affects physical and mental health. Mirtazapine (MTZ) is an effective medicine for treating depression, but patients lack compliance. However, transforming a pharmaceutical dosage form to an orodispersible film (ODF) could resolve this issue. This study aims to fabricate ODF-loading mirtazapine, using a syringe extrusion 3D printer, and compare its properties with the solvent-casting method. The ODFs were prepared by dissolving the mirtazapine in a hydroxypropyl methylcellulose E15 solution, and then fabricated by a 3D printer or casting. The 3D printing was accurate and precise in fabricating the ODFs. The SEM micrographs showed that the mirtazapine-printed ODF (3D-MTZ) was porous, with crystals of mirtazapine on the film’s surface. The 3D-MTZ exhibited better mechanical properties than the mirtazapine-casted ODF (C-MTZ), due to the 3D-printing process. The disintegration time of the 3D-MTZ in a simulated salivary fluid, pH 6.8 at 37 °C, was 24.38 s, which is faster than the C-MTZ (46.75 s). The in vitro dissolution study, in 0.1 N HCl at 37 °C, found the 3D-MTZ quickly released the drug by more than 80% in 5 min. This study manifested that 3D-printing technology can potentially be applied for the fabrication of ODF-containing mirtazapine.