Innovations in Chewable Formulations: The Novelty and Applications of 3D Printing in Drug Product Design

Since their introduction, chewable dosage forms have gained traction due to their ability to facilitate swallowing, especially in paediatric, geriatric and dysphagia patients. Their benefits stretch beyond human use to also include veterinary applications, improving administration and palatability in different animal species. Despite their advantages, current chewable formulations do not account for individualised dosing and palatability preferences. In light of this, three-dimensional (3D) printing, and in particular the semi-solid extrusion technology, has been suggested as a novel manufacturing method for producing customised chewable dosage forms. This advanced approach offers flexibility for selecting patient-specific doses, excipients, and organoleptic properties, which are critical for ensuring efficacy, safety and adherence to the treatment. This review provides an overview of the latest advancements in chewable dosage forms for human and veterinary use, highlighting the motivations behind their use and covering formulation considerations, as well as regulatory aspects

Temperature-Sensitive Gels for Intratumoral Delivery of β-Lapachone: Effect of Cyclodextrins and Ethanol

This work evaluated the potential of Pluronics (varieties F127 and P123) in combination with solubilizing agents to be used as syringeable in situ gelling depots of intratumoral β-lapachone (βLAP). Pluronic dispersions prepared at various concentrations in the absence and the presence of ethanol and randomly methylated β-cyclodextrin (RMβCD) were characterized regarding their rheological properties, drug solubilization capacity, and in vitro release. Pluronic F127 (18–23%) formulations combined high ability to solubilize βLAP (enhancement solubility factor up to 50), adequate gel temperature range (over 25°C), and gel strength at 37°C enough to guarantee the permanence of the formulation in the administration site for a period of time. βLAP release rate was finely tuned by the concentration of the polymer and the addition of RMβCD (diffusion coefficient ranging between 9 and 69 μg·cm−2). The ethanol increases βLAP release rate but simultaneously led to weak gels. This paper shows that βLAP formulations involving temperature-reversible Pluronic gels may be suitable for intratumoral drug delivery purposes

Synthesis of temperature-responsive Dextran-MA/PNIPAAm particles for controlled drug delivery using superhydrophobic surfaces

Purpose: To implement a bioinspired methodology using superhydrophobic surfaces suitable for producing smart hydro- gel beads in which the bioactive substance is introduced in the particles during their formation. Methods: Several superhydrophobic surfaces, including polystyrene, aluminum and copper, were prepared. Polymeric solutions composed by photo-crosslinked dextran-methacrylated and thermal responsive poly(N-isopropylacrylamide) mixed with a protein (insulin or albumin) were dropped on the superhydrophobic surfaces, and the obtained millimetric spheres were hardened in a dry environment under UV light. Results: Spherical and non-sticky hydrogels particles were formed in few minutes on the superhydrophobic surfaces. The proteins included in the liquid formulation were homogeneously distributed in the particle network. The particles exhibited temperature-sensitive swelling, porosity and protein release rate, with the responsiveness tunable by the dextran-MA/PNIPAAm weight ratio.Conclusions: The proposed method permitted the preparation of smart hydrogel particles in one step with almost 100% encapsulation yield. The temperature-sensitive release profiles suggest that the obtained spherical-shaped biomaterials are suitable as protein carriers. These stimuli-responsive beads could have potential to be used in pharmaceutical or other biomedical applications, including tissue engineering and regenerative medicine.The authors acknowledge funding from the project: PTDC/QUI/68804/2006 (FCT), IBEROMARE-Procept, FEDER and MICINN (SAF2008-01679). The research leading to these results has also received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement #NMP4-SL-2009-229292. The authors are grateful to project DISC REGENERATION, Collaborative Project-Large-scale integrating project, NMP3-LA-2008-213904 for the use of the UV lamp

Controlled Release of rAAV Vectors from APMA-Functionalized Contact Lenses for Corneal Gene Therapy

As an alternative to eye drops and ocular injections for gene therapy, the aim of this work was to design for the first time hydrogel contact lenses that can act as platforms for the controlled delivery of viral vectors (recombinant adeno-associated virus, rAAV) to the eye in an effective way with improved patient compliance. Hydrogels of hydroxyethyl methacrylate (HEMA) with aminopropyl methacrylamide (APMA) (H1: 40, and H2: 80 mM) or without (Hc: 0 mM) were synthesized, sterilized by steam heat (121 °C, 20 min), and then tested for gene therapy using rAAV vectors to deliver the genes to the cornea. The hydrogels showed adequate light transparency, oxygen permeability, and swelling for use as contact lenses. Loading of viral vectors (rAAV-lacZ, rAAV-RFP, or rAAV-hIGF-I) was carried out at 4 °C to maintain viral vector titer. Release in culture medium was monitored by fluorescence with Cy3-rAAV-lacZ and AAV Titration ELISA. Transduction efficacy was tested through reporter genes lacZ and RFP in human bone marrow derived mesenchymal stem cells (hMSCs). lacZ was detected with X-Gal staining and quantified with Beta-Glo®, and RFP was monitored by fluorescence. The ability of rAAV-hIGF-I-loaded hydrogels to trigger cell proliferation in hMSCs was evaluated by immunohistochemistry. Finally, the ability of rAAV-lacZ-loaded hydrogels to transduce bovine cornea was confirmed through detection with X-Gal staining of β-galactosidase expressed within the tissue

Imprinted contact lenses for sustained release of polymyxin B and related antimicrobial peptides

The aim of this work was to develop drug-soft contact lens combination products suitable for controlled release of antimicrobial peptides on the ocular surface. Incorporation of functional monomers and the application of molecular imprinting techniques were explored to endow 2-hydroxyethyl methacrylate (HEMA) hydrogels with the ability to load and to sustain the release of polymyxin B and vancomycin. Various HEMA–drug–functional monomer–cross–linker molar ratios were evaluated to prepare polymyxin B imprinted and non-imprinted hydrogels. Acrylic acid-functionalized and imprinted hydrogels loaded greater amounts of polymyxin B and led to more sustained release profiles, in comparison with non-functionalized and non-imprinted networks. Polymyxin B-loaded hydrogels showed good biocompatibility in hen’s egg test-chorioallantoic membrane tests. Functionalized hydrogels also loaded vancomycin and sustained its release, but the imprinting effect was only exhibited with polymyxin B, as demonstrated in rebinding tests. Microbiological assays carried out with Pseudomonas aeruginosa allowed identification of the most suitable hydrogel composition for efficient bacteria eradication; some hydrogels being able to stand several continued challenges against this important bacterial pathogen

Inkjet Printing of Pharmaceuticals

© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC), https://creativecommons.org/licenses/by-nc/4.0/Inkjet printing (IJP) is an additive manufacturing process that selectively deposits ink materials, layer-by-layer, to create 3D objects or 2D patterns with precise control over their structure and composition. This technology has emerged as an attractive and versatile approach to address the ever-evolving demands of personalized medicine in the healthcare industry. Although originally developed for nonhealthcare applications, IJP harnesses the potential of pharma-inks, which are meticulously formulated inks containing drugs and pharmaceutical excipients. Delving into the formulation and components of pharma-inks, the key to precise and adaptable material deposition enabled by IJP is unraveled. The review extends its focus to substrate materials, including paper, films, foams, lenses, and 3D-printed materials, showcasing their diverse advantages, while exploring a wide spectrum of therapeutic applications. Additionally, the potential benefits of hardware and software improvements, along with artificial intelligence integration, are discussed to enhance IJP's precision and efficiency. Embracing these advancements, IJP holds immense potential to reshape traditional medicine manufacturing processes, ushering in an era of medical precision. However, further exploration and optimization are needed to fully utilize IJP's healthcare capabilities. As researchers push the boundaries of IJP, the vision of patient-specific treatment is on the horizon of becoming a tangible reality.Peer reviewe

Layer-by-layer coated silicone-based soft contact lens hydrogel for diclofenac sustained release

Abstract in proceedings of the Fourth International Congress of CiiEM: Health, Well-Being and Ageing in the 21st Century, held at Egas Moniz’ University Campus in Monte de Caparica, Almada, from 3–5 June 2019.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.info:eu-repo/semantics/publishedVersio