Formulation Development of Antihypertensive Drug Labetalol HCL Injection

Labetalol Hydrochloride Injection USP (Labetalol hydrochloride) is an adrenergic receptor blocking agent possessing both alpha1 (post-synaptic) and beta-receptor blocking activity. Its action on beta-receptors is four times stronger than that on alpha-receptors. It antagonizes beta1- and beta2-receptors equally. The ratios of alpha- to beta-blockade differ depending on the route of administration estimated to be 1:3 (oral) and 1:7 (IV). Onset of action- Oral: 20 minutes to 2 hours; IV: Within 5 minutes. Peak effect: Oral: 2 to 4 hours; IV: 5 to 15 minutes. Duration of action- Oral: 8 to 12 hours (dose dependent), IV: Average: 16 to 18 hours (dose dependent). Half-Life Elimination -Oral: 6 to 8 hours; IV: ~5.5 hours. The parenteral route of Labetalol hydrochloride is considered as the best choice of route than compared to the oral route. In this introduction chapter discussed about parenteral dosage form, its significance, hypertension, mechanism of alpha beta blockers, advantages and disadvantages, different routes of administration, formulation of parenteral dosage form, evaluation of parenteral along with sterilization technique. And also briefly discussed about Preformulation studies of parenteral medications. The literature related to this work was surveyed and a brief discussion had been given on each literature in this chapter. The objective of the present formulation development was to develop a pharmaceutically acceptable, stable and reproducible generic formulation of Labetalol hydrochloride injection. The development studies were aimed at developing a drug product formulation matching the RLD (Reference listed drug) drug product characteristics and complying to the product characteristics listed in the USP monograph for of Labetalol hydrochloride injection. The method chapter covers the details of experimental methods, including Preformulation study, compatibility study, stress study along with evaluation study and finally stability study. The result chapter depicts the results for the all tests indicated in the method chapter. The results for all the parameter to be evaluated for the prepared of Labetalol hydrochloride injection and the Stability of the prepared formulation were given in this chapter. The discussion chapters deal with the optimization of the process and four formulation trials were taken for the optimization of process variables. The best trial was considered for further batches. The tests included in the study were performed with optimized batch and for each test separate batches were taken and study was conducted. The compatibility study with the containers, filters and tubings were tabulated. The prepared formulation was subjected to stress study with oxygen sensitivity, pH extremities, freeze thaw and photo stability and the results were found to be within the specification limits. Evaluation is the necessary step for parenteral and the solution to be injected should be free from any particulate matter to provide the sterile dosage form. The prepared injection provides all the compatibility for the quality control tests and found to be sterile. The prepared of Labetalol hydrochloride injection was assured for stability and it passes the stability criteria for that particular injection. The samples were analysed after withdrawal of the sample from stability chamber and all the test parameters was carried out accordingly and the sample passes all the test criteria and the results was found to be within specification. Labetalol is a unique parenteral that competitively blocks alpha- and beta-adrenergic receptors. The main objective of the study was to formulate a safe and stable Labetalol Hydrochloride Injection USP (labetalol hydrochloride) with the dose of 5 mg/ mL. Drug, methyl paraben, propyl paraben, EDTA, dextrose, order of mixing was determined in pre-formulation development. Based on D-value, moist-heat sterilization method (121°C for 20 mins) is chosen for the developed injection formulation. The Process compatibility study reveals that injection potency and purity did not affected when exposed to stainless steel and process tubing. The filter compatibility study demonstrates that the Labetalol Hydrochloride Injection passes through filter without having drug loss due to binding of the drug to the membrane. Stability study of developed formulation conducted at Nitrogen purged environment, different pH, and various temperatures are tested over time for the amount of drug, methylparaben, propylparaben, EDTA, impurities, and particulate matter clearly indicated the drug product was stable. Labetalol Hydrochloride injection passes the entire quality control release test and there were no mechanical issues during the process. Thus, the product can be manufactured at a large scale

Physicochemical properties of p-hydroazobenzene: a nonlinear optical crystal

138-142Crystal of p-hydroazobenezene was grown and the crystal system is confirmed by analysis the XRD data. The material delineated in monclinic system with the space group of Pbca. FTIR and Raman spectrum analysis have been performed to comprehend the molecular interactions and to learn the vibrational nature of the functional groups in the title compound. Optical, and thermal stability analysis were also been carried out. Exhaustive explorations were conducted on the optical properties of the crystal using both quantum chemical calculations and experimental data

Physicochemical properties of p-hydroazobenzene: a nonlinear optical crystal

Crystal of p-hydroazobenezene was grown and the crystal system is confirmed by analysis the XRD data. The material delineated in monclinic system with the space group of Pbca. FTIR and Raman spectrum analysis have been performed to comprehend the molecular interactions and to learn the vibrational nature of the functional groups in the title compound. Optical, and thermal stability analysis were also been carried out. Exhaustive explorations were conducted on the optical properties of the crystal using both quantum chemical calculations and experimental data

A Catalytic Spectrophotometric Method for the Analytical Determination of Trace Amounts of Mercury (II)

Abstract A catalytic method has been developed for the determination of microgram amounts of mercury (II) based on its catalytic effect on the rate of a ligand substitution reaction. The reaction studied involved the substitution of cyanide in hexacyanoferrate (II) by resacetophenone benzoic acid hydrazone (2', 4'-dihydroxy propiophenone benzoic acid hydrazone) and the reaction was monitored spectrophotometrically. Satisfactory results were obtained for the determination of mercury (II) in the range 0.1086-0.9774 µg/ml. The relative standard deviation was less than 2.1%. The method detection limit and limit of quantification was found to be 0.041 µg/ml and 0.083 µg/ml respectively (n=7). The correlation coefficient for the determination was found to be 0.9989. The effect of foreign ions on the determination was studied

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2\ub75th percentile and 100 as the 97\ub75th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59\ub74 (IQR 35\ub74–67\ub73), ranging from a low of 11\ub76 (95% uncertainty interval 9\ub76–14\ub70) to a high of 84\ub79 (83\ub71–86\ub77). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of 'leaving no one behind', it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990-2017, projected indicators to 2030, and analysed global attainment. METHODS: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0-100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

© 2018 The Author(s). Background: Assessments of age-specifc mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Afairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. Methods: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specifc mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in diferent components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. Findings: Globally, 18·7% (95% uncertainty interval 18·4-19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2-59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5-49·6) to 70·5 years (70·1-70·8) for men and from 52·9 years (51·7-54·0) to 75·6 years (75·3-75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5-51·7) for men in the Central African Republic to 87·6 years (86·9-88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3-238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6-42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2-5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. Interpretation: This analysis of age-sex-specifc mortality shows that there are remarkably complex patterns in population mortality across countries. The fndings of this study highlight global successes, such as the large decline in under-5 mortality, which refects signifcant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing