Designing of the ibuprofen mucoadhesive film for relief the oral pain and inflammation

زمینه و هدف: اشکال مخاط چسب، از سیستم های دارورسانی جدید هستند که بصورت قرص و فیلم موجودند. فیلم مخاط چسب دهانی زمان توقف دارو را طولانی می کند و یک شیب بالای غلظتی برای نفوذ ارائه می دهد که منجر به بهبود جذب دارو می شود. هدف از این مطالعه تهیه سیستم تحویل منطقه ای داروی ایبوپروفن به منظور تسکین درد و التهاب خفیف تا متوسط دهانی از طریق تهیه ی فرمولاسیون مخاط چسب دهان بود. روش بررسی: در این مطالعه تجربی فیلم های مخاط چسب ایبوپروفن با روش Casting و با بکارگیری ترکیبات مختلفی از پودر یودراژیت ((EUDRAGIT RL100 و سدیم کربوکسیل متیل سلولوز (NaCMC) به عنوان پلیمر و گلیسرین و پروپیلن گلیکول به عنوان پلاستی سایزر تهیه و از نظر ویژگی‌های ظاهری و فارماسیوتیکسی مانند ظاهر، وزن، ضخامت، قدرت چسبندگی، زمان آزادسازی، زمان از هم پاشیدگی و قدرت بارگیری دارو در فیلم بررسی شدند. داده ها با استفاده از آزمون آماری آنالیز واریانس و تست تعقیبی توکی در نرم افزار SPSS مورد تجزیه و تحلیل قرار گرفتند. یافته ها: سرعت آزاد سازی دارو در فرمولاسیون های مختلف مورد بررسی تفاوت زیادی نشان نداد. استفاده از یودراژیت به میزان بیشتر از 1000 میلی گرم موجب افزایش ویسکوزیته سیستم و کاهش خلل و فرج و ظاهر مناسب فیلم شد اما فیلم‌های ساخته شده با یودراژیت و NaCMC از نظر ویژگی‌های ظاهری و فارماسیوتیکسی قابل قبول تر بودند. نتیجه گیری: بهترین فرمولاسیون با چسبندگی مناسب و سرعت آزادسازی مورد نظر شامل 35 میلی گرم ایبوپروفن، 200 میلی گرم NaCMC و1500 میلی گرم یودراژیت بود که به دلیل ویسکوزیته بالا، قدرت چسبندگی مناسب، نوسانات کم در آزادسازی دارو (در طول 4 ساعت) به عنوان فرمولاسیون برتر انتخاب شد؛ لذا به نظر می رسد این شکل دارویی بتواند مورد توجه و استفاده ی بسیاری از بیماران قرار گیرد

Use of lipophilic and hydrophilic polymers in production of sustained release zinc sulfate tablets

Background and aims: Zinc sulfate administered to correct zinc deficiency. Its oral administration has shown serious digestive side effects and sometimes it has led to the lack of use it. The main aim of the present study was to use lipophilic and hydrophilic polymers in production of sustained release zinc sulfate tabletsover an extended period of time. Methods: Sustained release (SR) zinc sulfate tablets were prepared using either lipophilic-based matrix or hydrophilic matrix system or natural polymers by either hot-fusion (HF) granulation or direct compression (DC) method. Physical and chemical features of provided SR tablets including hardness, friability, and weight variation, disintegration time, swelling index, content uniformity and drug release behavior were evaluated. The drug concentration was assayed by an atomic absorption spectrophotometer at 213.8 nm. Results: Most of the prepared formulations showed acceptable physicochemical properties. Among 30 formulations, SR tablets with lipophilic matrix-based showed more predictable release profiles compared to tablets prepared based on hydrophilic or natural matrixes. Tablets containing carnauba wax showed slower release while tablets with hydrogenated castor oil represented faster release profile. A few lipophilic matrix tablets containing zinc sulfate (110 mg), beeswax (or carnauba wax) and Avicel (or Emcompress) were selected as the optimum formulations showing release profiles based on USP criteria for lipophilic-based SR tablets. The mean dissolution time (MDT) and dissolution efficiency (DE8%) of selected formulations were 1.69-1.95 hr and 69.3-71.8%, respectively. Tablet hardness and granule size had no effects on release rate. The drug release kinetic followed Higuchi model. Conclusion: Lipophilic based SR tablets of zinc sulfate is suggested as an alternative for capsule or syrup of the drug whichhave digestive side effects

Development and Evaluation of a Novel Pellet-Based Tablet System for Potential Colon Delivery of Budesonide

Budesonide, a potent glucocorticoid, is used for the treatment of inflammatory bowel diseases. Current available oral formulations of budesonide have low efficacy against ulcerative colitis because of the premature drug release in the upper part of the gastrointestinal tract. In this paper a pH- and time-controlled colon-targeted pellet-based tablet of budesonide was established. Pellet cores were prepared by extrusion-spheronization method and further coated with xanthan gum (barrier layer), Eudragit NE30D and L30D55 combination (inner layer), and Eudragit FS30 (as enteric layer) sequentially to achieve the required release profile. The coated pellets then compressed into tablets using inert tabletting granules of Cellactose or Pearlitol. Release studies, performed in simulated gastric, intestinal, and colon pH were used in sequence to mimic the gastrointestinal transit. The influence of formulation variables like barrier layer thickness, inner layer composition, and enteric coat thickness on drug release were investigated and the coated pellets that contained 12% weight gain in xanthan gum layer, Eudragit L30D55 and Eudragit NE30D with a ratio of 3 : 7 in inner layer with 30% weight gain and 25% weight gain in Eudragit FS layer were found to protect the drug release in stomach and small intestine and 83.35 ± 2.4 of budesonide was released at 24 h. The drug release from the tablets prepared using 40% Cellactose 80 as tableting excipient was found to be closely similar to that of uncompressed pellets

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding Bill & Melinda Gates Foundation

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Calcium Acetate Versus Calcium Carbonate as Oral Phosphate Binder: Preparation and In Vitro Assessment: Calcium acetate as oral phosphate binder

Calcium acetate is used as an oral phosphate binder to control hyperphosphatemia in patients with chronic renal failure. Compared to calcium carbonate,control of hyperphosphatemia can be achieved at lower calcium administration with calcium acetate which likely reduces the risk of hypercalcemia. In this study,various formulations of calcium acetate tablets were prepared and their disintegration times, dissolution rates and phosphate binding capacities were determined. Dissolution test was carried out using the paddle method according to the United States Pharmacopoeia (USP XXIII). The binding efficiency of the tablets was compared by measuring the amount of insoluble phosphate after mixing with a sodium phosphate solution at pH 6. Calcium acetate tablets had a mean content of 809.6 mg of calcium acetate and a mean weight of 1087 mg. The average breaking load and disintegration times were 66.4±5.5 N and 24.5±2.1 min, respectively. Drug release after 30 and 60 min were 80.45% and 101.42%, respectively. The amount of nondissolved phosphorus following 60 min incubation of calcium acetate and/or calcium carbonate tablets were 372.8 mg (61.2%) and 463.2 mg (76.0%), respectively.Weight variation, friability, disintegration time, and dissolution rate of calciumacetate tablets were in the acceptable pharmacopoeial limits. Ahigh phosphate bindingcapacity of calcium acetate tablets indicated that it can be a suitable alternative tocalcium carbonate in the management of hyperphosphatemia in patients withchronic renal failure

Designing Fuzzy Inference System by Learning from Training Samples to Measure the Participation of Operational Staff in the Health of Workplace

To achieve the highest level of health in organizations, there is a need to create a proper space for active participation of staff. To enable this partnership, organizations need tools to measure participation to determine deviations, in order to revise their programs. This research aimed to design a system for measuring employee participation in workplace health regardless of the estimation of non-linear relationships between the effective variables. For this purpose, we designed a Fuzzy Inference System. Employees' participation scores and predisposing factors involved in health respectively, considered as output and input of the system. Rules have been created by using modified CT08 method based on training samples. In the end, we created 17 rules and the system was tested with 5 prototypes. It should be noted that the accuracy rate was 92.3 percent. The researchers also suggested changes in calculation of accuracy rate which made the rate more realistic