FORMULATION AND EVALUATION OF FAST DISSOLVING TABLETS OF AMOXYCILLIN TRIHYDRATE AND POTASSIUM CLAVULANATE

Objective: The present work is aimed to formulate fast dissolving stable tablet formulation a preferred combination of Amoxycillin trihydrate (Beta-lactum antibiotic) and Potassium clavulanate (Beta-lactum inhibitor) by using various super disintegrants.Methods: Fast dissolving tablets are prepared by direct compression method using super disintegrants i.e. sodium starch glycolate, crospovidone, croscarmellose sodium. Aspartame as a sweetener and trusil mango flavor were used to increase palatability. Reduction in the dose of Amoxycillin trihydrate and Potassium clavulanate tablet was possible by developing fast dissolving tablet. Results: The powder blends were subjected to various pre-formulation evaluations such as, tapped density, bulk density, hausner's ratio, the angle of repose and compressibility index. The prepared Amoxycillin trihydrate and Potassium clavulanate fast dissolving tablets were evaluated for thickness, weight variation, friability, disintegration time, hardness, wetting time and in vitro drug release. All fast dissolving tablet formulations shown uniform weight, hardness and friability data indicates the good mechanical resistance of the fast dissolving tablet. Fast dissolving tablets were disintegrated between 25-50 second and in vitro disintegration time of the best fast disintegrating tablets was found to be 25 second. Conclusion: Amoxycillin trihydrate and Potassium clavulanate fast dissolving tablets were found to be of good quality fulfilling all the needs for fast dissolving tablets. The optimised (F-4) formulation had shown best disintegration time and released profile with a maximum in vitro drug release as compare to marketed preparation at all time intervals of in vitro drug release

FAST DISSOLVING TABLETS: A REVIEW

Fast dissolving tablets emerge as one of the popular and widely accepted dosage forms, especially for pediatric patients because of incomplete development of the muscular and nervous system and a case of geriatric patients suffering from Parkinson's disorder or hand tremors. Few solid dosage forms like capsules and tablets are present days facing the problems like difficulty in swallowing (dysphagia), resulting in many incidences of non-compliance and making the therapy ineffective. Oral dosage form and oral route are the most preferred route of administration for various drugs have limitations like first-pass metabolism, psychiatric patients, bedridden and uncooperative patients. FDTs are disintegrating or dissolve quickly in the saliva without a need of water. Fast dissolving tablets are designed to dissolve in saliva remarkably faster, within a few seconds (less than 60 seconds), and those are real fast-dissolving tablets. FDTs formulations contain super disintegrants to enhance the disintegration rate of a tablet in the buccal cavity. FDTs have advantages such as easy portability and manufacturing, accurate dosing, good chemical and physical stability and an ideal alternative for geriatric and pediatric patients. FDTs have disintegrated quickly, absorb faster so, in vitro drug release time improve and this property of drugs (dosage form) enhanced bioavailability. FDT formulations have the advantage of both conventional tablet formulation and liquid dosage form. There are several technologies that are conventional or patented based on spray drying, cotton candy process, sublimation, melt granulation, direct compression freezes drying/lyophilization, phase transition process, mass extrusion, etc. have been developed for manufacturing of FDTs. In this review contain brief information about FDTs including definition, advantages, needs or requirements of FDTs, salient features of FDTs, limitations, challenges to developing FDT, marketed formulations of fast dissolving tablets, etc

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Temporal and Seasonal Variations of the Hot Spring Basin Hydrothermal System, Yellowstone National Park, USA

Monitoring Yellowstone National Park’s hydrothermal systems and establishing hydrothermal baselines are the main goals of an ongoing collaborative effort between Yellowstone National Park’s Geology program and Utah State University’s Remote Sensing Services Laboratory. During the first years of this research effort, improvements were made in image acquisition, processing and calibration. In 2007, a broad-band, forward looking infrared (FLIR) camera (8–12 microns) provided reliable airborne images for a hydrothermal baseline of the Hot Spring Basin hydrothermal system. From 2008 to 2011, night-time, airborne thermal infrared image acquisitions during September yielded temperature maps that established the temporal variability of the hydrothermal system. A March 2012 airborne image acquisition provided an initial assessment of seasonal variability. The consistent, high-spatial resolution imagery (~1 m) demonstrates that the technique is robust and repeatable for generating corrected (atmosphere and emissivity) and calibrated temperature maps of the Hot Spring Basin hydrothermal system. Atmospheric conditions before and at flight-time determine the usefulness of the thermal infrared imagery for geohydrologic applications, such as hydrothermal monitoring. Although these ground-surface temperature maps are easily understood, quantification of radiative heat from the Hot Spring Basin hydrothermal system is an estimate of the system’s total energy output. Area is a key parameter for calculating the hydrothermal system’s heat output. Preliminary heat calculations suggest a radiative heat output of ~56 MW to 62 MW for the central Hot Spring Basin hydrothermal system. Challenges still remain in removing the latent solar component within the calibrated, atmospherically adjusted, and emissivity corrected night-time imagery

MRI Staging of Anorectal Malignancy—A Reporting Dilemma: Is It Adenocarcinoma or Squamous Cell Carcinoma?

Aim Magnetic resonance imaging (MRI) of anorectal malignancy is often reported assuming low rectal adenocarcinoma (LRC). The biopsy may, however, reveal squamous cell carcinoma (SCC). Thus, the aim was to compare the imaging findings of SCC and LRC. Methods This was a retrospective study of patients who underwent staging MRI for anorectal malignancy (<5 cm from the anal verge) for adenocarcinoma or squamous cell carcinoma between 2016 and 2021. Two radiologists blinded to biopsy reviewed MRI. Imaging findings and apparent diffusion coefficient (ADC) values were compared between SCC and LRC. Results We studied 137 patients (n = 60 SCC, n = 77 LRC) with a mean age of 50.4 (standard deviation: 12.4) years and tumor length of 5.6 ± 1.9 cm. SCC patients were older, and their distal tumor margin was closer to the anal verge (5.3 vs. 22 mm for LRC; p <0.001). T2 intermediate signal and diffusion restriction was seen in 97 and 98.2% of SCC and 75.3 and 77% of LRC, respectively. SCC had lower ADC values (0.910 × 10−3 mm2/s) than LRC (1.126 × 10−3 mm2/s; p < 0.001). But there was no difference in the ADC values when T2 hyperintense tumors were excluded (p = 0.132). Extramural vascular invasion (EMVI) was more frequent in LRC (35.1 vs. 16.7%; p = 0.013). A combination of distance from the anal verge of less than 11 mm, absent EMVI, and the presence of internal iliac and inguinal nodes had an area under the curve (95% confidence interval) of 0.810 (0.737–0.884). Conclusion ADC values are unhelpful in differentiating SCC and LRC. Tumors closer to anal verge, absence of EMVI, and the presence of inguinal and internal-iliac nodes may point towards SCC

Predicting Positive Radial Margin on Restaging MRI of Patients with Low Rectal Cancer: Can We Do Better?

Objective The aim of this study was to characterize the tissue involving the margin and study if this information will affect margin prediction on restaging magnetic resonance imaging (MRI) in low rectal adenocarcinoma (LRC) patients treated with neoadjuvant long-course chemoradiotherapy (LCCRT)

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Predictors of Outcomes in Patients With Mild Ischemic Stroke Symptoms: MaRISS

Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3–5. Few symptomatic intracerebral hemorrhages were recorded (<1%). Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3–5 subgroup. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02072681