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Biotinidase deficiency is a rare inherited disorder characterized by biotin metabolism issues, leading to neurological and cutaneous symptoms that can be alleviated through biotin administration. Three-dimensional (3D) printing (3DP) offers potential for personalized medicine production for rare diseases, due to its flexibility in designing dosage forms and controlling release profiles. For such point-of-care applications, rigorous quality control (QC) measures are essential to ensure precise dosing, optimal performance, and product safety, especially for low personalized doses in preclinical and clinical studies. In this work, we addressed QC challenges by integrating a precision balance into a direct powder extrusion pharmaceutical 3D printer (M3DIMAKER™) for real-time, in-line mass uniformity testing, a critical quality control step. Small and large capsule-shaped biotin printlets (3D printed tablets) for immediate- and extended-release were printed. The integrated balance monitored and registered each printlet's weight, identifying any deviations from acceptable limits. While all large printlet batches met mass uniformity criteria, some small printlet batches exhibited weight deviations. In vitro release studies showed large immediate-release printlets releasing 82% of biotin within 45 min, compared to 100% for small immediate-release printlets. For extended-release formulations, 35% of the drug was released from small printlets, whereas 24% was released from large printlets at the same time point. The integration of process analytical technology tools in 3DP shows promise in enhancing QC and scalability of personalized dosing at the point-of-care, demonstrating successful integration of a balance into a direct powder extrusion 3D printer for in-line mass uniformity testing across different sizes of capsule-shaped printlets., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alvaro Goyanes reports a relationship with FABRX Ltd. that includes: employment and equity or stocks. Abdul Basit reports a relationship with FABRX Ltd. that includes: equity or stocks. Carlos Rial reports a relationship with FABRX AI Ltd. that includes: employment. Carlos Bendicho-Lavilla reports a relationship with FABRX Ltd. that includes: employement. Corresponding author part of the editorial board in International Journal of Pharmaceutics − A.B. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Diffusion cells play a crucial role in the pharmaceutical and cosmetic fields by assessing the release and permeation of active pharmaceutical ingredients across membranes. However, commercially available glass-based devices, such as Franz diffusion cells, are expensive and fragile. The emergence of three-dimensional (3D) printing technology enables the creation of diffusion cells with cost-effective polymeric materials and resins, offering exceptional precision and custom geometries. Nonetheless, there are challenges associated with interactions between 3D printing materials and drug molecules. This work aimed to develop inert coatings for 3D-printed diffusion models. Diffusion devices were designed and 3D-printed with a stereolithography (SLA) 3D printer, and different coatings were applied. Then, two model drugs were used to evaluate drug retention by coated devices. Among the tested coatings, one of them showed great potential in preventing drug retention and was selected for subsequent experiments with different drugs and conditions. Finally, voriconazole eyedrops were used to confirm the viability of 3D-printed Franz diffusion cells as a drug release diffusion model. The favourable results obtained with the coating promote the use of 3D printing as a cost-effective manufacturing technology, capable of producing diffusion cells tailored to specific study requirements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Despite the high success rates of dental implants, peri-implantitis is currently the most common complication in dental implantology. Peri-implantitis has an inflammatory nature, it is associated with the accumulation of plaque in the peri-implant tissues, and its evolution can be progressive depending on various factors, comorbidities, and poor oral health. Prophylaxis and different treatment methods have been widely discussed in recent decades, and surgical and non-surgical techniques present both advantages and disadvantages. In this work, a literature review of different studies on the application of adjuvant treatments, such as local and systemic antibiotics and antiseptic treatments, was conducted. Positive outcomes have been found in the short (up to one year after treatment) and long term (up to ten years after treatment) with combined therapies. However, there is still a need to explore new therapies based on the use of advanced drug delivery systems for the effective treatment of peri-implantitis in the long term and without relapses. Hence, micro- and nanoparticles, implants, and injectable hydrogels, among others, should be considered in future peri-implantitis treatment with the aim of enhancing overall therapy outcomes.

Chronic retinal diseases, such as age-related macular degeneration (AMD), are a major cause of global visual impairment. However, current treatment methods involving repetitive intravitreal injections pose financial and health burdens for patients. The development of controlled drug release systems, particularly for biological drugs, is still an unmet need in prolonging drug release within the vitreous chamber. To address this, green supercritical carbon dioxide (scCO 2 ) foaming technology was employed to manufacture porous poly(lactic-co-glycolic acid) (PLGA)-based intravitreal implants loaded with dexamethasone. The desired implant dimensions were achieved through 3D printing of customised moulds. By varying the depressurisation rates during the foaming process, implants with different porosities and dexamethasone release rates were successfully obtained. These implants demonstrated controlled drug release for up to four months, surpassing the performance of previously developed implants. In view of the positive results obtained, a pilot study was conducted using the monoclonal antibody bevacizumab to explore the feasibility of this technology for preparing intraocular implants loaded with biologic drug molecules. Overall, this study presents a greener and more sustainable alternative to conventional implant manufacturing techniques, particularly suited for drugs that are susceptible to degradation under harsh conditions., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Fungal keratitis (FK) is a corneal mycotic infection that can lead to vision loss. Furthermore, the severity of FK is aggravated by the emergence of resistant fungal species. There is currently only one FDA-approved formulation for FK treatment forcing hospital pharmacy departments to reformulate intravenous drug preparations with unknown ocular bioavailability and toxicity. In the present study, natamycin/voriconazole formulations were developed and characterized to improve natamycin solubility, permanence, and safety. The solubility of natamycin was studied in the presence of two cyclodextrins: HPβCD and HPγCD. The HPβCD was chosen based on the solubility results. Natamycin/cyclodextrin (HPβCD) inclusion complexes characterization and a competition study between natamycin and voriconazole were conducted by NMR (Nuclear Magnetic Resonance). Based on these results, several eye drops with different polymer compositions were developed and subsequently characterized. Permeability studies suggested that the formulations improved the passage of natamycin through the cornea compared to the commercial formulation Natacyn ® . The ocular safety of the formulations was determined by BCOP and HET-CAM. The antifungal activity assay demonstrated the ability of our formulations to inhibit the in vitro growth of different fungal species. All these results concluded that the formulations developed in the present study could significantly improve the treatment of FK.

Biodegradable poly(lactic-co-glycolic acid) microspheres (PLGA MSs) are attractive delivery systems for site-specific maintained release of therapeutic active substances into the intravitreal chamber. The design, development, and characterization of idebenone-loaded PLGA microspheres by means of an oil-in-water emulsion/solvent evaporation method enabled the obtention of appropriate production yield, encapsulation efficiency and loading values. MSs revealed spherical shape, with a size range of 10-25 μm and a smooth and non-porous surface. Fourier-transform infrared spectroscopy (FTIR) spectra demonstrated no chemical interactions between idebenone and polymers. Solid-state nuclear magnetic resonance (NMR), X-ray diffractometry, differential scanning calorimetry (DSC) and thermogravimetry (TGA) analyses indicated that microencapsulation led to drug amorphization. In vitro release profiles were fitted to a biexponential kinetic profile. Idebenone-loaded PLGA MSs showed no cytotoxic effects in an organotypic tissue model. Results suggest that PLGA MSs could be an alternative intraocular system for long-term idebenone administration, showing potential therapeutic advantages as a new therapeutic approach to the Leber's Hereditary Optic Neuropathy (LHON) treatment by intravitreal administration., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Diabetes mellitus is a major health problem with increasing prevalence at a global level. The discovery of insulin in the early 1900s represented a major breakthrough in diabetes management, with further milestones being subsequently achieved with the identification of glucagon-like peptide-1 (GLP-1) and the introduction of GLP-1 receptor agonists (GLP-1 RAs) in clinical practice. Moreover, the subcutaneous delivery of biotherapeutics is a well-established route of administration generally preferred over the intravenous route due to better patient compliance and prolonged drug absorption. However, current subcutaneous formulations of GLP-1 RAs present pharmacokinetic problems that lead to adverse reactions and treatment discontinuation. In this review, we discuss the current challenges of subcutaneous administration of peptide-based therapeutics and provide an overview of the formulations available for the different routes of administration with improved bioavailability and reduced frequency of administration., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)