SUSTAINED RELEASE ITOPRIDE HYDROCHLORIDE MATRIX TABLET

Oral route gets the highest priority for thedelivery of the drug as well as better patient compliance incase of self delivery dosage formulation. The aim ofpresent investigation was undertaken with the objective offormulating sustain release formulation of Itopridehydrochloride for oral drug delivery. Itopride hydrochlorideis highly water soluble prokinetic drug.Hydroxypropylmethylcellulose K4M (lower viscositygrade) and K100M (higher viscosity grade) were used as amatrix forming agents to control the release of drug. HPMCK4M and HPMC K100M were used individually as well asin combination with different proportion in the preparationof the Sustained release formulation. 32 factorial designswere applied to the polymer concentration that affects thedrug release profile. Reduced equation for drug release at2hr,6hr,and10hrwere22 1 2 1 Q 37.644 5.41X 3.25X 2.017X ,26 1 2 1 Q 72.367 8.05X 4.4X 3.75X ,and10 1 1 2 90.844 5.8 2.633 2.8 2 Q X X X Xrespectively. Optimized batch F019 shows good tabletproperties like hardness(7-9kg/cm2), thickness(4.48mm),friability(0.024%),assay(99.3%) and nearly similar drugrelease profile to the targeted reference drug release profileand it was indicated by similarity factor (f2=86.04)

Development and Validation of HPTLC Method for Simultaneous Quantification of Dapagliflozin and Vildagliptin in Tablet Dosage Form

In recent times, the combination of Dapagliflozin and Vildagliptin has emerged as a therapeutic option for managing diabetes. This study presents the development of a rapid, selective, sensitive, and robust high-performance thin-layer chromatography (HPTLC) method for the simultaneous quantification of Dapagliflozin (DAPA) and Vildagliptin (VILG) in both their pure forms and in a commercially available formulation. The separation was successfully achieved on silica gel F254, utilizing a solvent system composed of Toluene: Ethyl Acetate: Methanol: Ammonia (6.0: 2.0: 2.0: 0.1, v/v/v/v). Chromatographic bands were visualized under short-wave ultraviolet light at 217 nm. The proposed technique demonstrated well-defined spots for DAPA and VILG, with retention factor Rf values of 0.54 and 0.28, respectively. The method exhibited good linearity within concentration ranges of 200–1400 ng/band for DAPA and 2000-14000 ng/band for VILG. The developed method was successfully applied to the marketed formulation of tablets containing combined dosage form of DAPA and VILG.&nbsp

Solid self-emulsifying drug delivery system of Furosemide

The aim of the present investigation was to prepare and optimize solid self-emulsifying drug delivery system (S-SEDDS) of Furosemide, which is poorly water soluble drug. Solubility of furosemide was performed in different oils, surfactants, co-surfactants and co-solvents. Selection of these ingredients in liquid Self Emulsifying Formulation was done on the bases of solubility and pseudo ternary phase diagram. The selected ingredients were - Capmul MCM C8 was as oil which also has properties of co-surfactants, Tween 80 as surfactant and PEG 400 as co-solvent. Prepared liquid Self Emulsifying Formulation was converted in to solid powder with the help of PEG 6000, micro crystalline cellulose PH 102. The solid powder with liquid SEF was compressed into tablet prepared tablets were evaluated for different pre-compression, post compression evaluation parameters. The formula for tablet was optimized by using 32 factorial design. The results of in-vitro drug release data of optimized batch showed drastically improved dissolution rate of Furosemide. The results of accelerated stability study of optimized batch indicated that the optimized formulation was stabl

Matrix sustained release tablet of water soluble prokinetic agent: Itopride Hydrochloride

Itopride hydrochloride is highly water soluble prokinetic drug that is used in the Gastro esophageal reflux disease (GERD). Aim of present investigation was formulating sustained release formulation of Itopride hydrochloride for oral drug delivery. Oral route gets the highest priority for the delivery of the drug as well as better patient compliance in case of self medication. Pregelatinized Starch, Hydroxy methyl propyl cellulose (HPMC) K4M, HPMC K100M and Ethyl Cellulose were used to control the release of the drug from the sustained release tablet. Optimization of polymers concentration that can control the release of the drug as like the hypothetical release profile was based on trial and error. Optimized batch F11 was showing good tablet properties like hardness (7-8kg/cm2), thickness (4.61mm), friability (0.061%), assay (99.3%) and nearly similar drug release profile to the hypothetical drug release profile and it was indicated by similarity factor (F2=80.25). Mathematical model application was applied to the release profile of optimized batch. The obtained value of regression coefficient was 0.9962 which indicate that formulation was following the higuchi mode

Evaluation of whey protein concentrate as a functional ingredient on quality of goat milk rasogolla - an Indian dessert

In the literature, a variety of dairy products are made from goat milk; however, information related to the manufacture of rasogolla from goat milk is very scant. During preliminary trials, it was observed that chhena prepared from goat milk was not suitable for the preparation of rasogolla because it has a very soft and sticky body that is difficult to handle. Therefore, this investigation was conducted to formulate an acceptable quality goat milk rasogolla using whey protein concentrate (WPC) as a functional ingredient. Chhena (also known as Indian cottage cheese, a heat- and acid-coagulated indigenous dairy product) was prepared from fresh Surati goat milk (3.5% fat/8.5% milk solids-not-fat (MSNF). Twelve batches of rasogolla were prepared from chhena coagulated at three temperatures viz. 75, 80 and 85⁰C containing WPC at 4 levels (i.e., 0, 0.25, 0.50 and 0.75% w/w of milk). Rasogolla prepared from chhena containing 0.50% WPC in milk  and coagulated at 80°C was preferred the most with respect to all the sensory attributes evaluated. It had significantly (P<0.05) highest sucrose content, i.e., 35.73% and a higher sugar absorption ratio, i.e., 2.63, compared to all the other experimental samples. The composition of drained samples of goat milk rasogolla was as follows: moisture 50.07%; protein 7.04%; fat 6.44%; ash 0.45% and sucrose 35.73%. The pH was 6.34 and acidity was 0.76% lactic acid. Based on the results obtained in this study, a method was developed for the preparation of acceptable quality goat milk chhena and rasogolla

Electronics design and development of Near-Infrared Imager, Spectrometer and Polarimeter

NISP, a multifaceted near-infrared instrument for the upcoming 2.5m IR telescope at MIRO Gurushikhar, Mount Abu, Rajasthan, India is being developed at PRL, Ahmedabad. NISP will have wide (FOV = 10' x 10') field imaging, moderate (R=3000) spectroscopy and imaging polarimetry operating modes. It is designed based on 0.8 to 2.5 micron sensitive, 2048 X 2048 HgCdTe (MCT) array detector from Teledyne. Optical, Mechanical and Electronics subsystems are being designed and developed in-house at PRL. HAWAII-2RG (H2RG) detector will be mounted along with controlling SIDECAR ASIC inside LN2 filled cryogenic cooled Dewar. FPGA based controller for H2RG and ASIC will be mounted outside the Dewar at room temperature. Smart stepper motors will facilitate motion of filter wheels and optical components to realize different operating modes. Detector and ASIC temperatures are servo controlled using Lakeshore's Temperature Controller (TC) 336. Also, several cryogenic temperatures will be monitored by TC for health checking of the instrument. Detector, Motion and Temperature controllers onboard telescope will be interfaced to USB Hub and fiber-optic trans-receiver. Remote Host computer interface to remote end trans-receiver will be equipped with in-house developed GUI software to control all functionalities of NISP. Design and development aspects of NISP Electronics will be presented in this conference.Comment: 6 pages, 3 figures, Submitted to SPIE Conference Astronomical Telescopes + Instrumentation 202

A novel, dominant disease mechanism of distal renal tubular acidosis with specific variants in <i>ATP6V1B1</i>

Background and hypothesis:ATP6V1B1 encodes a subunit of the vacuolar H+-ATPase and pathogenic variants are associated with autosomal recessive distal renal tubular acidosis (dRTA) with deafness. Heterozygous variants predicted to affect a specific amino acid, Arg394, have been recurrently reported in dRTA but their significance has been unclear. We hypothesised that these variants are associated with a dominant disease mechanism.Methods:Retrospective analysis of cases identified in our genetic laboratories and through European nephrology organisations. Data regarding demographics, clinical presentation, laboratory findings, hearing and imaging studies of kidneys were collected from the index patient and, if available, from other family members. The potential disease mechanism was investigated through structural modelling in silico.Results:Twenty index patients in total were included, of which 19 carried the variant c.1181G&gt;A; p.(Arg394Gln) and one c.1180C&gt;G; p.(Arg394Gly). In 7 families, more than one member was affected and the variant segregated with the disease in those with available information (15 affected, 6 unaffected), except for the unaffected mother of 2 affected children, who was mosaic. In no patient was a second causative variant in trans identified. In 8 sporadic patients and 1 affected parent, the variant was confirmed to be de novo. Both variants are absent in gnomAD. Sensorineural hearing loss was reported in 8 of the 22 patients with available information. Structural modelling supports a crucial role for Arg394 in nucleotide binding.Conclusion:We provide strong evidence for the pathogenicity of heterozygous variants affecting Arg394 and thus a novel inheritance modus for ATP6V1B1-associated dRTA. Clinically, this form differs from the recessive one by the lower prevalence of hearing loss. The prominent position of Arg394 in the nucleotide binding fold of the H+-ATPase structure is consistent with a dominant negative mechanism. Our findings inform the diagnosis and management of patients with dRTA and variants of Arg394

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. METHODS: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. FINDINGS: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. INTERPRETATION: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. FUNDING: Bill & Melinda Gates Foundation