Development And Evaluation Of Prolonged Release Ketoprofen Tablets

Suatu sistem perlepasan terpanjang telah dibangunkan menggunakan salutan filem sebagai sistem perlepasan terpanjang drug dan ketoprofen telah digunakan sebagai drug model. A prolonged release system was developed using film coating as drug release controlling system and ketoprofen as model drug

Development and stability evaluation of olive oil nanoemulsion using sucrose ester

Nanoemulsion is a type of emulsion that consist of fine oil-in-water dispersions, with the droplets covering the size range of 20-200nm. It can be achieved through self-emulsification process. One of the processes is through low energy emulsification method. Olive oil was chosen in this study due to its efficiency in treating skin problem. Pre-emulsion was prepared by mixing oil, sucrose ester and glycerol under heat at 80 °C. After the pre-emulsion was formed, it will be self-emulsified with water under gentle agitation. Olive oil nanoemulsion was prepared using sucrose ester as a surfactant to produce droplets size below 200 nm with low size distribution. The pre-emulsion was very stable when stored at 4 “C. However, it was unstable when stored at 25 °C and 40 °C. Therefore, 4 °C is the ideal storage condition for this pre-emulsion

Optimal synthesis of energy efficiency improvement for NGLS indirect sequence fractionation unit

Once natural gas liquids (NGLs) have been separated from natural gas stream, they are further separated into their component parts, or fractions, using a distillation process known as fractionation. Distillation is the primary separation process widely used in the natural gas processing. Although it has many advantages, the main drawback is its large energy requirement, which can significantly influence the overall plant profitability. Another question that needs to be answered here is there any systematic study and analysis to improve energy saving for the NGLs fractionation plant without having major modifications to the separation units, which is more practical to implement. The large energy requirement of these processes can be systematically reduced by determining the optimal sequence using driving force method. Therefore, the objective of this paper is to present the study and analysis of the energy saving improvement for the NGLs fractionation plant by using driving force method which will require only minor or less modifications to the separation units. Generally, the concept of driving force was applied in designing an energy efficient distillation column [Gani and Bek-Pedersen, 2004]. However, the concept has been extended its application in designing energy efficient distillation columns sequence [Mustafa et. al., 2014]. To perform the studies and analysis, the energy efficient NGLs fractionation plant methodology is developed. Basically, the methodology consists of four hierarchical steps. In the first step, the energy that is obtained from the base NGLs sequence will be used as guidance for the next step where the base NGLs sequence is developed from a simple and reliable short-cut method. In the second step, the energy efficiency in distillation column will be improved through driving force method where the optimum sequence will be determined in this step. In the third step, the optimum sequence was analyzed in term of energy analysis by using a simple and reliable shortcut method distillation column in Aspen HYSYS environment. In the final step, the comparison between the existing sequence and the optimum sequence by using driving force method will be done and at the same time the economic performance for the optimum sequence is also evaluated in this step. Then, the return of investment (ROI) will be calculated to make sure that the proposed modification to improve energy saving is practical. The capability of this methodology is tested in designing an optimal energy efficient distillation columns sequence of NGLs fractionation unit. The existing NGLs fractionation unit consists of nine compounds (methane, ethane, propane, i-butane, nbutane, i-pentane, n-pentane, n-hexane, n-heptane) with direct-splitter-direct sequence was simulated using a simple and reliable short-cut method within Aspen HYSYS environment. A total of 519.68 MW energy used to achieve 99.9% of product recovery. A new optimal sequence determined by driving force method was simulated using a short-cut method within Aspen HYSYS environment where a total of 376.60 MW of energy was used of the same product recovery. The results show that the maximum of 27.53 % energy reduction was able to achieve by changing the sequence suggested by the driving force method. It can be concluded that, the sequence determined by the driving force method is able to reduce energy used for NGLs fractionation. All of this findings show that the methodology is able to design energy efficient distillation columns for NGLs fractionation sequence in an easy, practical and systematic manner

Usage of sugar ester in the preparation of avocado oil nanoemulsion

Objectives: Due to the high dynamics of pharmaceutical products markets, developments of new products using latest innovative technology are becoming a norm of many pharmaceutical companies. Nanoscale materials such as nanoemulsion (NE) offer advantages such as the controllable droplet size, long-term stability, and power solubilization ability. It is beneficial in various delivery systems either for transdermal, ocular, nasal, vaginal, and parenteral drug delivery. The objective of the study was to prepare avocado oil NE using different surfactants to find the most suitable nanosized droplets, as avocado oil offers a variety of purported nutritional and medicinal benefits. Methods: Sucrose esters, glycerol, and avocado oil with different ratio were used to produce pre-NE by phase inversion technique then pre-NE were self-emulsified with water to produce NE. The influence of the sucrose esters surfactants on the NE formulations were determined using three different types of sucrose esters surfactant (laureate, oleate, and palmitate). Stability study was conducted for NE at different temperatures (4°C, 25°C, and 40°C) for 6 months. Results: The NE contained sucrose laureate produced best nanosized formulations compared to other oleate and palmitate, with optimum droplet size 106 ± 1.70 nm, size distribution 0.156 ± 0.01, and zeta potential -30.4 ± 0.70. The NE formulations were very stable at 4°C compared to 25°C and 40°C while at 25°C NE showed moderate stability, but it was unstable at 40°C. Conclusion: Sucrose laureate was able to produce NE with phase inversion and self-emulsification techniques and the ideal storage condition for NE is 4°C

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Improvement of anti-inflammation of swietenia macrophylla self nanoemulsion

Nowadays there is an intensely usage of natural bioactive materials as medicinal agent in pharmaceutical industries. Swietenia macrophylla (SM) has been reported to have biological activities such as anti-inflammatory, anti-mutagencity, anti-fungal and anti-tumor activities. Therefore, SM oil was used in the formulation of oral nanoemulsion as self-nanoemulsifying system and topical nanoemulsion as nanoemulgel. In this study, self-nanoemulsifying formulations were prepared for both SM and olive oils using different surfactants/co-surfactants nonionic surfactants (Labrasol, Tween 20, Capmul and Labrafil). For topical preparation, nanoemulgels of SM and olive oils were prepared, first by mixing the oil, glycerol with sucrose ester (Laureate, Oleate and Palmitate) to produce pre-nanoemulsion by heat inversion technique. Then nanoemulsion was formed upon the mixing with water by selfemulsification technique. After that Carbopol (934 and 940) was added to nanoemulsion to produce the nanoemulgel. Finally safety and pharmacology studies were conducted for the prepared formulations. The acute and sub-acute toxicity studies were conducted for SM oil self-nanoemulsifying system on rats. The biochemical parameters were evaluated by studying serum alanine transferase (ALT), aspartate transferase (AST) and alkaline phosphatase (ALP). The histopathology of the rats liver sections were studied under light microscope after staining with haematoxylin and eosin. On the other hand, the anti-inflammatory property for SM oil was screened using carrageenan induced rat paw edema method for SM oil for both oral (self-nanoemulsifying system) and topical (nanoemulgel) preparations. The optimal self-nanoemulsifying formulations were prepared using Tween20/Labrafil (2:1) and Capmul/Labrasol (1:2), producing small droplets size of <150 nm, low polydispersity index below 0.3 and relatively good stability with zeta potential lower than -30. It was found that 50% oil with sucrose laureate (20%) and glycerol (30%) was able to produce a very stable nanoemulsion when stored at 4 °C with droplets size less than 150 nm, with low size distribution below 0.2 and low zeta potential -40. The optimal nanoemulsion formulation was mixed with water and different grades of Carbopol (934 and 940) to produce nanoemulgel. It was found that 0.5% Carbopol 940 produces a stable nanoemulgel and it showed high stability when stored at different temperatures 4 °C, 25 °C and 40 °C for one year with no significant influence on the oil droplets size, size distribution and zeta potential. In addition, the anti-inflammatory properties of Swietenia macrophylla oil were greater in the form of self-nanoemulsifying system and nanoemulgel than in the oil solution. Swietenia macrophylla oil in the form of self-nanoemulsifying system possesses no toxicity effect on rats after acute and sub-acute studies. In conclusion, Swietenia macrophylla oil showed a safety profile with improvement in the anti-inflammatory activity with the help of nanoemulsion