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In the current study hollow microneedles (HMNs) were fabricated by means of vat polymerization method for the transdermal delivery of insulin. Two geometries of HMNs were designed in a Computer Aided Design (CAD) software namely, curved pyramid and syringe-like and fabricated with Liquid Crystal Display (LCD) method. Dimensions were determined and quality features were imaged with scanning electron microscopy (SEM). Volumetric characterization of HMNs and microchannels was performed by microfocus computed tomography (μCT) whereas mechanical characterization and skin penetration tests of the two geometries were carried out both experimentally and by Finite Element Analysis (FEA) simulation. Diffusion studies of insulin across full thickness human skin were performed in vitro using Franz diffusion cells. Insulin samples were analyzed with liquid chromatography-mass spectrometry (LC-MS). The results show that the transport might be affected by the shape of the microneedles.

The main objective of this study was to investigate the mechanical behavior of 3D printed fiberglass-reinforced nylon honeycomb structures. A Continuous Fiber Fabrication (CFF) 3D printer was used since it makes it possible to lay continuous strands of fibers inside the 3D printed geometries at selected locations across the width in order to optimize the bending behavior. Nylon and nylon/fiberglass honeycomb structures were tested under a three-point bending regime. The microstructure of the filaments and the 3D printed fractured surfaces following bending tests were examined with Scanning Electron Microscopy (SEM). The modulus of the materials was also evaluated using the nanoindentation technique. The behavior of the 3D printed structures was simulated with a Finite Element Model (FEM). The experimental and simulation results demonstrated that 3D printed continuous fiberglass reinforcement is possible to selectively adjust the bending strength of the honeycombs. When glass fibers are located near the top and bottom faces of honeycombs, the bending strength is maximized.

The present study aimed to fabricate a hollow microneedle device consisting of an array and a reservoir by means of 3D printing technology for transdermal peptide delivery. Hollow microneedles (HMNs) were fabricated using a biocompatible resin material, while PLA filament was used for the reservoirs. The fabricated microdevice was characterized by means of optical microscopy, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), contact angle measurements and leakage inspection studies to ensure the passageway of liquid formulations. Mechanical failure and penetration tests were carried out and supported by Finite Element Analysis (FEA). The cytocompatibility of the microneedle arrays was assessed to human keratinocytes (HaCaT). Finally, the transport of the model peptide octreotide acetate across artificial membranes was assessed in Franz cells using the aforementioned HMN design.

Child-appropriate dosage forms are critical in promoting adherence and effective pharmacotherapy in pediatric patients, especially those undergoing long-term treatment in low-resource settings. The present study aimed to develop orodispersible films (ODFs) for isoniazid administration to children exposed to tuberculosis. The ODFs were produced from the aqueous solutions of natural and semi-synthetic polymer blends using electrospinning. The spinning solutions and the resulting fibers were physicochemically characterized, and the disintegration time and isoniazid release from the ODFs were assessed in simulated salivary fluid. The ODFs comprised of nanofibers with adequate thermal stability and possible drug amorphization. Film disintegration occurred instantly upon contact with simulated salivary fluid within less than 15 s, and isoniazid release from the ODFs in the same medium followed after the disintegration profiles, achieving rapid and total drug release within less than 60 s. The ease of administration and favorable drug loading and release properties of the ODFs may provide a dosage form able to facilitate proper adherence to treatment within the pediatric patient population.

In pharmaceutical formulations, pharmacokinetic behavior of the Active Pharmaceutical Ingredients (API's) is significantly affected by their dissolution profiles. In this project, we attempted to create personalized dosage forms with osmotic properties that exhibit different API release patterns via Fused Deposition Modelling (FDM) 3D printing. Specifically, cellulose acetate was employed to create an external shell of an osmotically active core containing Diltiazem (DIL) as model drug. By removing parts of the shell (upper surface, linear lateral segments) were created dosage forms that modify their shape at specific time frames under the effect of the gradually induced osmotic pressure. Hot-Melt Extrusion (HME) was employed to fabricate two different 3DP feeding filaments, for the creation of either the shell or the osmotic core (dual-extrusion printing). Printed formulations and filaments were characterized by means of (TGA, XRD, DSC) and inspected using microscopy (optical and electron). The mechanical properties of the filaments were assessed by means of micro- and macro mechanical testing, whereas micro-Computed Tomography (μCT) was employed to investigate the volumetric changes occurring during the hydration process. XRD indicated the amorphization of DIL inside HME filaments and printed dosage forms, whereas the incorporated NaCl (osmogen) retained its crystallinity. Mechanical properties’ testing confirmed the printability of produced filaments. Dissolution tests revealed that all formulations exhibited sustained release differing at the initiation time of the API dissolution (0, 120 and 360 min for the three different formulations). Finally, μCT uncovered the key structural changes associated with distinct phases of the release profile. The above results demonstrate the successful utilization of an FDM 3D printer in order to create osmotic 3D printed formulations exhibiting sustained and/or delayed release, that can be easily personalized containing API doses corresponding to each patient's specific needs.

Customization of pharmaceutical products is a central requirement for personalized medicines. However, the existing processing and supply chain solutions do not support such manufacturing-on-demand approaches. In order to solve this challenge, three-dimensional (3D) printing has been applied for customization of not only the dose and release characteristics, but also appearance of the product (e.g., size and shape). A solution for customization can be realized via non-expert-guided processing of digital designs and drug dose. This study presents a proof-of-concept computational algorithm which calculates the optimal dimensions of grid-like orodispersible films (ODFs), considering the recommended dose. Further, the algorithm exports a digital design file which contains the required ODF configuration. Cannabidiol (CBD) was incorporated in the ODFs, considering the simple correspondence between the recommended dose and the patient's weight. The ODFs were 3D-printed and characterized for their physicochemical, mechanical, disintegration and drug release properties. The algorithm was evaluated for its accuracy on dose estimation, highlighting the reproducibility of individualized ODFs. The in vitro performance was principally affected by the thickness and volume of the grid-like structures. The concept provides an alternative approach that promotes automation in the manufacturing of personalized medications in distributed points of care, such as hospitals and local pharmacies.

Personalized drug delivery systems are considered an interesting perspective of the 3D printing technology, with the potential to counterbalance the pharmacological and adverse effects of pharmaceutical products. Our study was focused on the utilization of the pressure-assisted microsyringes technology to fabricate patient-tailored lidocaine-loaded suppositories. Printable inks were fabricated using a combination of an oily compound with a mixture of surfactants and evaluated for the physicochemical properties, as well as for their resemblance to the performance of self-nanoemulsifying drug delivery systems (SNEDDS). The selected ink composition was loaded with lidocaine (LID) in two concentrations (2 w/w % and 4 w/w %), showing droplet sizes in the range between 31.0 ± 8.4 nm and 42.7 ± 13.5 nm, respectively, and negative surface charge. The physicochemical characterization revealed the presence of LID in the amorphous state. The mechanical properties and in vitro performance of the SNEDDS-like suppositories complied with the European Pharmacopoeia requirements. The in vitro dissolution profiles evidenced the delayed LID released in the case of 2 w/w % LID-loaded suppositories. The work highlighted the potential of 3D printing as an alternative pathway to formulate personalized LID-loaded suppositories for local anesthesia.