Hot-melt extruded in situ gelling systems (MeltDrops Technology): Formulation development, in silico modelling and in vivo studies.

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.

Nebulizer systems: a new frontier for therapeutics and targeted delivery.

Drug delivery via the pulmonary route is a cornerstone in the pharmaceutical sector as an alternative to oral and parenteral administration. Nebulizer inhalation treatment offers multiple drug administration, easily employed with tidal breathing, suitable for children and elderly, can be adapted for severe patients and visible spray ensures patient satisfaction. This review discusses the operational and mechanical characteristics of nebulizer delivery devices in terms of aerosol production processes, their usage, benefits and drawbacks that are currently shaping the contemporary landscape of inhaled drug delivery. With the advent of particle engineering, novel inhaled nanosystems can be successfully developed to increase lung deposition and decrease pulmonary clearance. The above-mentioned advances might pave the path for treating a life-threatening disorder like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is also discussed in the current state of the art.

Preparation and Evaluation of N-Trimethyl Chitosan Nanoparticles of Flurbiprofen for Ocular Delivery.

PURPOSE: A major challenge in ocular therapeutics is poor bioavailability of drug, 1% or even less of the instilled dose is absorbed and frequent administration of conventional products leads to poor adherence to therapy. Hence, the present study is to synthesize N-trimethyl chitosan (TMC), a water-soluble chitosan derivative and to prepare flurbiprofen (FLU):hydroxyl propyl-ß-cyclodextrin (HP-ß-CD) complex-loaded nanoparticles for treatment of bacterial conjunctivitis which aims to increase the residence time in ocular tissue, thus enhancing patient compliance and improved efficacy. METHODS: TMC was synthesized and characterized by 1H NMR and FT-IR. TMC and chitosan (CS) nanoparticles containing inclusion complex were prepared by ionic gelation using sodium tripolyphosphate (TPP). The nanoparticles thus obtained were evaluated for particle size, zeta potential, drug entrapment, in-vitro release, in-vitro mucoadhesion, and TEM for morphology and irritation potential was evaluated by the HET-CAM technique. RESULTS: N-methyl quaternization of CS was confirmed by 1H NMR. The particle size and zeta potential of the TMC nanoparticles were found to be 201 ± 1.55 nm and +13.9 ± 1.697 mV and that of CS nanoparticles were 361.2 ± 1.55 nm and +10.9 ± 0.424 mV, respectively. The entrapment of FLU- HP-ß-CD inclusion complex in polymeric nanoparticles was found to be 10.91 ± 1.541%. The observed in-vitro release profile of TMC nanoparticles indicated characteristic burst release followed by delayed release. HET-CAM studies demonstrated the ocular safety of TMC nanoparticles. CONCLUSION: The developed TMC nanoparticles offered prolonged release potential for transmucosal ocular delivery of hydrophobic flurbiprofen.