QbD-Based Stability-Indicating RP-HPLC Method Development and Validation for the Estimation of Favipiravir-An Eco-Friendly Approach.

BACKGROUND: Analytical quality by design (AQbD) affords a systematic scaffolding to triumph a continuously validated, robust assay as well as life cycle management. The resuscitative repurposed drug favipiravir, an oral drug approved for reemerging pandemic influenza in Japan in 2014, is used for the treatment of life-threatening pathogens such as Ebola, Lassa virus, and currently COVID-19. Favipiravir is gaining a great deal of medical importance due to its pharmaceutical applications. OBJECTIVE: To develop and validate a risk-based stability-indicating RP-HPLC method employing an AQbD approach using Central Composite Design (Design Expert Software 13.0) for the estimation of favipiravir. METHOD: The Quality Target Product Profile optimized were flow rate and mobile phase composition, thus assessing the critical analytical attributes (retention time, tailing factor, and number of theoretical plates) as the constraints of method robustness. The proposed technique was optimized with a C18 (150 × 4.6 mm, 5 µm) column and 0.1% orthophosphoric acid buffer-acetonitrile (50:50, v/v) as the mobile phase at a flow rate of 1 mL/min using diode-array detector (230 nm) eluted favipiravir at 2.3 min. RESULTS: The optimized method validated as per ICH guideline Q2 (R1) was found to be eco-friendly, simple, precise (RSD 0.0051-1.2%), accurate (99.86-100.22%), linear (25-150 µg/mL), rugged (RSD 0.70%), and robust (RSD 0.6-1.6%) with a limit of detection and limit of quantitation of 1.140 µg/mL and 4.424 µg/mL, respectively. CONCLUSION: Forced degradation studies (acidic, alkaline, thermal, photolytic, and oxidative conditions) revealed the suitability of the AQbD method for the analysis of favipiravir in tablet formulation.The developed and validated AQbD method is less time consuming and can be used in the industry for routine quality control/analysis of bulk drug and marketed Favipiravir products. HIGHLIGHTS: A robust Design of Experiment enhanced stability-indicating analytical method was developed and validated for the estimation of favipiravir. Furthermore, the contemporary method would aid in extending the analysis of favipiravir in other formulations.

Microplastics as an emerging threat to the freshwater ecosystems of Veeranam lake in south India: A multidimensional approach.

In the current scenario, microplastic, as a contaminant, is becoming an ecological threat to the freshwater ecosystem. The present study attempted to determine the quality and quantity of microplastic contaminants in water and soil samples at Veeranam lake in Tamil Nadu, India. It is very important to mention that the Veeranam lake in Tamil Nadu, is a major urban water source of the capital district of Tamil Nadu. Using Van Veen grab-sampling equipment and trawl methods, the study detected the presence of microplastics in 28 sediment samples and 31 water samples from the collected samples. In addition to this, the density separation was performed with zinc chloride solution using the Sediment-Microplastic Isolation (SMI) unit. The quantum of total plastic particle present in surface water were in the range of 13-54 items/km2 with a mean value of 28 items/km2. In the case of sediment samples, the amount of total plastic particle was found in the range of 92-604 items/kg with a mean value of 309 items/kg. The abundance of microplastic particles in water and sediments in various shape, colour, and composition as in the order of nylons > polythene > fibres/PVC > fragments > foam > pellets; dominant colours as white > red > black > green > blue and yellow at the sampling sites. In term of percentage of contaminant distribution, the study found that the collected water and sediment samples deposited with polymer type of plastic particles were nylon (39%), polyethylene (23%), polystyrene (19%), polypropylene (15%), and polyvinyl chloride (4%). The research work is a baseline study for the proposed site of Veeranam lake for microplastics contamination.

Two-year treatment outcomes of patients enrolled in India's national first-line antiretroviral therapy programme.

BACKGROUND: We aimed to analyse treatment outcomes of patients receiving first-line antiretroviral therapy (ART) through the national AIDS control programme of India. METHODS: Using routinely collected programme data, we analysed mortality, CD4 evolution and adherence outcomes over a 2-year period in 972 patients who received first-line ART between 1 October 2004 and 31 January 2005 at 3 government ART centres. Cox regression analysis was used to identify independent predictors of mortality. RESULTS: Of the 972 patients (median age 35 years, 66% men), 71% received the stavudinellamivudine/nevirapine regimen. The median CD4 count of enrolled patients was 119 cells/cmm (interquartile range [IQR] 50-200 cells/ cmm) at treatment initiation; 44% had baseline CD4 count <100 cells/cmm. Of the 927 patients for whom treatment outcomes were available, 71% were alive after 2 years of treatment. The median increase in CD4 count was 1 42 cells/ cmm (IQR 57-750 cells/cmm; n=616) at 6 months and 184 cells/cmm (IQR 102-299 cells/cmm; n=582) at 12 months after treatment. Over 2 years, 124 patients (13%) died; the majority of deaths (68%) occurred within the first 6 months of treatment. Those with baseline CD4 count <50 cells/cmm were significantly more likely to die (adjusted hazard ratio 2.5, 95% confidence interval 1.3-3.2) compared with patients who had baseline CD4 count >50 cells/cmm. Over the 2-year period, 323 patients (35%) missed picking up their monthly drugs at least once and 147 patients (16%) were lost to follow up. CONCLUSION: Survival rates of HIV-infected patients on first-line ART in India were comparable with those from other resource-limited countries. Most deaths occurred early and among patients who had advanced disease. Earlier initiation of HIV treatment and improving long term treatment adherence are key priorities for India's ART programme.

Lumping and splitting: the health policy agenda in India.

India's health system was designed in a different era, when expectations of the public and private sectors were quite different. India's population is also undergoing transitions in the demographic, epidemiologic and social aspects of health. Disparities in life expectancy, disease, access to health care and protection from financial risks have increased. These factors are challenging the health system to respond in new ways. The old approach to national health policies and programmes is increasingly inappropriate. By analyzing inter- and intra-state differences in contexts and processes, we argue that the content of national health policy needs to be more diverse and accommodating to specific states and districts. More 'splitting' of India's health policy at the state level would better address their health problems, and would open the way to innovation and local accountability. States further along the health transition would be able to develop policies to deal with the emerging epidemic of non-communicable diseases and more appropriate health financing systems. States early in the transition would need to focus on improving the quality and access of essential public health services, and empowering communities to take more ownership. Better 'lumping' of policy issues at the central level is also needed, but not in ways that have been done in the past. The central government needs to focus on overcoming the large inequalities in health outcomes across India, tackle growing challenges to health such as the HIV epidemic, and provide the much needed leadership on systemic issues such as the development of systems for quality assurance and regulation of the private sector. It also needs to support and facilitate states and districts to develop critical capacities rather than directly manage programmes. As India develops a more diverse set of state health policies, there will be more opportunities to learn what works in different policy environments.

Maternal and fetal indicators of oxidative stress in various obstetric complications.

The present study demonstrates the incidence of increased lipid peroxidation and protein oxidation in both maternal and fetal erythrocytes as markers of oxygen radical activity in different complications of pregnancy. In fetuses born after premature rupture of membranes, lipid peroxidation was significantly elevated as indicated by increased malondialdehyde levels (p<0.05) as compared to controls. Proteolytic activity in the erythrocytes of mothers in this group was also significantly high (p<0.01). In patients delivered by lower segment cesarian section, lipid peroxidation and proteolytic activity in maternal erythrocytes were significantly high (p<0.05 and p<0.001 respectively). In patients with prolonged second stage of labour, lipid peroxidation and proteolytic activity in maternal erythrocytes was significantly higher than in controls (p<0.001 and p<0.05 respectively). In this group, endogenous protein damage due to oxidative stress was significantly high both in the mother and the fetus (p<0.001 and p<0.05 respectively).