DEVELOPMENT AND IN VITRO–IN VIVO EVALUATION OF GASTRORETENTIVE FLOATING TABLETS OF AN ANTIRETROVIRAL AGENT RITONAVIR

Objective: The present research work concerns the development of the extended release of Ritonavir floating matrix tablets, designed to prolong the gastric residence time, increase the drug bioavailability, and diminish the side effects of irritating drugs. Methods: The floating tablets of Ritonavir were prepared by direct compression method using different grades of hydroxypropyl methylcellulose (HPMC), crospovidone, Polyox WSR 303, and sodium bicarbonate, as gas generating agent. Evaluation parameters and in vivo radiographic studies were conducted in suitable model. Results: Among all formulations, F21 was chosen as optimized formulation based on evaluation parameters such as floating lag time (33 s), total floating time (>24 h), and in vitro dissolution studies. From in vitro dissolution studies, the optimized formulation F21 and marketed product were shown 98.67% and 91.46±5.02% of drug release, respectively. The main appliance of medication discharge follows zero-order kinetics and non- Fickian transport by coupled diffusion and erosion. In vivo experiments maintained the potentials in extending the gastric residence time in the fasted state in beagle dogs. The mean gastric residence time of the optimized formulation found to be 330 min±40 in the stomach, where longer gastric residence time is an important condition for prolonged or controlled drug release and also for enhanced bioavailability. Conclusion: From in vitro and in vivo radiographic studies, Ritonavir floating tablets estimated to provide novel choice for harmless, inexpensive, and extended release for the effective management of AIDS

An improved liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of dexmedetomidine concentrations in samples of human plasma

Dexmedetomidine (DMET) is a sedative, analgesic and anxiolytic with minimum adverse respiratory effects. An LC-MS/MS bioanalytical method has been developed and validated to accurately measure DMET concentrations in samples of human plasma. The method overcomes difficulties in the extraction and quantification of DMET due to the fact that it binds strongly to glass and plastic tubes, as well as solid phase extraction (SPE) cartridges. Human plasma (50 μL) was mixed with the internal standard (IS) (DMET-d4) solution (100 μL) and 0.1% formic acid (50 μL) and extracted using Oasis HLB 1 CC (30 mg) solid phase extraction (SPE) cartridges (Waters®). The glass tubes were coated with bovine serum albumin (BSA) 0.5% (20 μL) before eluting DMET and the IS. After evaporation under nitrogen at room temperature, the analytes were reconstituted in 20% acetonitrile in 0.1% formic acid in water and transferred to silanized glass vials. An electrospray ionisation (ESI) mass spectrometry method in positive mode was created and the precursor/product transitions (m/z) were 201.1 → 95.0 (DMET) and 204.9 → 99.0 (IS). The method was robust and fully validated based on the 2012 EMEA guideline for bioanalytical method validation in the concentration range of 0.5-20 ng/mL. Using this assay, we showed that DMET binds strongly to Extracorporeal Membrane Oxygenation (ECMO) circuits, consistent with expectations for small lipophilic compounds

Extracorporeal life support devices and strategies for management of acute cardiorespiratory failure in adult patients: A comprehensive review

Evolution of extracorporeal life support (ECLS) technology has added a new dimension to the intensive care management of acute cardiac and/or respiratory failure in adult patients who fail conventional treatment. ECLS also complements cardiac surgical and cardiology procedures, implantation of long-term mechanical cardiac assist devices, heart and lung transplantation and cardiopulmonary resuscitation. Available ECLS therapies provide a range of options to the multidisciplinary teams who are involved in the time-critical care of these complex patients. While venovenous extracorporeal membrane oxygenation (ECMO) can provide complete respiratory support, extracorporeal carbon dioxide removal facilitates protective lung ventilation and provides only partial respiratory support. Mechanical circulatory support with venoarterial (VA) ECMO employed in a traditional central/peripheral fashion or in a temporary ventricular assist device configuration may stabilise patients with decompensated cardiac failure who have evidence of end-organ dysfunction, allowing time for recovery, decision-making, and bridging to implantation of a long-term mechanical circulatory support device and occasionally heart transplantation. In highly selected patients with combined severe cardiac and respiratory failure, advanced ECLS can be provided with central VA ECMO, peripheral VA ECMO with timely transition to venovenous ECMO or VA-venous ECMO upon myocardial recovery to avoid upper body hypoxia or by addition of an oxygenator to the temporary ventricular assist device circuit. This article summarises the available ECLS options and provides insights into the principles and practice of these techniques. One should emphasise that, as is common with many emerging therapies, their optimal use is currently not backed by quality evidence. This deficiency needs to be addressed to ensure that the full potential of ECLS can be achieved

Provision of ECPR during COVID-19: evidence, equity, and ethical dilemmas

The use of extracorporeal cardiopulmonary resuscitation (ECPR) to restore circulation during cardiac arrest is a time-critical, resource-intensive intervention of unproven efficacy. The current COVID-19 pandemic has brought additional complexity and significant barriers to the ongoing provision and implementation of ECPR services. The logistics of patient selection, expedient cannulation, healthcare worker safety, and post-resuscitation care must be weighed against the ethical considerations of providing an intervention of contentious benefit at a time when critical care resources are being overwhelmed by pandemic demand

The impact of acute lung injury, ECMO and transfusion on oxidative stress and plasma selenium levels in an ovine model

The purpose of this study was to determine the effects of smoke induced acute lung. injury (S-ALI), extracorporeal membrane oxygenation (ECMO) and transfusion on oxidative stress and plasma selenium levels. Forty ewes were divided into (i) healthy control (n = 4), (ii) S-ALI control (n = 7), (iii) ECMO control (n = 7), (iv) S-ALI + ECMO (n = 8) and (v) S-ALI + ECM + packed red blood cell (PRBC) transfusion (n = 14). Plasma thiobarbituric acid reactive substances (TBARS), selenium and glutathione peroxidase (GPx) activity were analysed at baseline, after smoke injury (or sham) and 0.25, 1, 2, 6, 7, 12 and 24 h after initiation of ECMO. Peak TBARS levels were similar across all groups. Plasma selenium decreased by 54% in S-ALI sheep (1.36 +/- 0.20 to 0.63 +/- 0.27 mu mol/L, p < 0.0001), and 72% in sheep with S-ALI + ECMO at 24 h (1.36 +/- 0.20 to 0.38 +/- 0.19, p < 0.0001). PRBC transfusion had no effect on TBARS, selenium levels or glutathione peroxidase activity in plasma. While ECMO independently increased TBARS in healthy sheep to levels which were similar to the S-ALI control, the addition of ECMO after S-ALI caused a negligible increase in TBARS. This suggests that the initial lung injury was the predominant feature in the TBARS response. In contrast, the addition of ECM in S-ALI sheep exacerbated reductions in plasma selenium beyond that of S-ALI or ECM alone. Clinical studies are needed to confirm the extent and duration of selenium loss associated with ECMO. Crown Copyright (C) 2015 Published by Elsevier GmbH. All rights reserved

Letter to the editor regarding Extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis

10.1186/s13054-021-03702-6CRITICAL CARE25