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[Display omitted] In situ gelling systems (ISGS) can prolong retention time and bioavailability of ophthalmic solutions. The complexity and cost of ISGS avert their industrial scale-up and clinical implementation. In this study, we demonstrate novel application of hot-melt extrusion (HME) technology for continuous manufacturing of ISGS (MeltDrops Technology). Timolol maleate (TIM) and dorzolamide hydrochloride (DRZ) loaded MeltDrops were successfully developed using HME for glaucoma management, thereby resolving issues with batch manufacturing of ISGS, prolonging retention time thus improving bioavailability. The MeltDrops technology involves one-step, i.e., passing all the ingredients through an extruder at a screw speed between 20 and 50 rpm and barrel temperature of 80 °C. The comparative evaluation of MeltDrops and batch-processed ISGS demonstrated that MeltDrops exhibited better physical and chemical content uniformity. The extrusion temperature and screw speed were critical factors influencing content uniformity and properties of the MeltDrops. MeltDrops showed sustained drug release for > 12 h in vitro (TIM = 83.07%; DRZ = 60.43%, 12 h) versus marketed eyedrops. The developed MeltDrops followed Peppas-Sahlin model, combining Fickian diffusion and swelling processes. The in vivo study in New Zealand rabbits revealed superior effectiveness and safety of the MeltDrops as compared to the marketed eyedrops. Herein we conclude, MeltDrops would serve as a cutting-edge platform technology that can be used to manufacture various ISGS with one-step processability, cost-effectiveness, and improved product quality, which are otherwise processed by batch manufacturing that involves numerous complex processing steps. [ABSTRACT FROM AUTHOR]

Human respiratory syncytial virus (RSV) is a major cause of acute respiratory infection. In 2020, RSV was eliminated from New Zealand due to non-pharmaceutical interventions (NPI) used to control the spread of SARS-CoV-2. However, in 2021, following a brief quarantine-free travel agreement with Australia, there was a large-scale nationwide outbreak of RSV that led to reported cases more than five-times higher than typical seasonal patterns. We generated 1470 viral genomes of both RSV-A and RSV-B sampled between 2015-2022 from across New Zealand. Using a phylodynamics approach, we used these data to better understand RSV transmission patterns in New Zealand prior to 2020, and how RSV became re-established in the community following the relaxation of COVID-19 restrictions. We found that in 2021, there was a large epidemic of RSV due to an increase in importations, leading to several large genomic clusters of both RSV-A ON1 and RSV-B BA9 genotypes. However, while a number of viral importations were detected, there was also a major reduction in RSV genetic diversity compared to pre-pandemic years. These data reveal the impact of NPI used during the COVID-19 pandemic on other respiratory infections and highlight the important insights that can be gained from viral genomes., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)