Application of Quality by Design Principles to Study the Effect of Coprocessed Materials in the Preparation of Mirtazapine Orodispersible Tablets.

The aim of this study was to determine the effect of two coprocessed materials in presence and absence of superdisintegrant (kyron T314) in the preparation of mirtazapine orodispersible tablets. Mirtazapine solubility was increased by complexation with kleptose forming an inclusion complex in a ratio 1:1. Quality by Design (QbD) was incorporated to determine the material attributes and the critical quality attributes (CQAs). Box behnken design was applied to study the effect of three independent variables X1: amount of lufiflash, X2: amount of pearlitol flash and X3: % of kyron T314 on two responses, Y1: dissolution after 1 minute and Y2: disintegration time. All formulated ODTs showed disintegration time less than 35 seconds and all formulations showed a notable increase in dissolution rate. Design space was determined from the overlay plot of different variables, X1 and X2 and X3 at two levels of the superdisintegrant. The one with maximum predicted dissolution rate and minimum predicted disintegration time was a formulation containing ludiflash (X1)= 9.25 mg, pearlitol flash (X2= 50 mg) and kyron T314= 3%. This formulation (Test ODT) was prepared and was subjected to in vivo study. Mirtazapine in human plasma was determined by LC-MS/MS and different pharmacokinetic parameters was determined for both test ODT and conventional oral tablet (Remeron). The pharmacokinetic parameters indicated that the two formulations are bioequivalence

Application of Quality by Design Principles to Study the Effect of Coprocessed Materials in the Preparation of Mirtazapine Orodispersible Tablets.

The aim of this study was to determine the effect of two coprocessed materials in presence and absence of superdisintegrant (kyron T314) in the preparation of mirtazapine orodispersible tablets. Mirtazapine solubility was increased by complexation with kleptose forming an inclusion complex in a ratio 1:1. Quality by Design (QbD) was incorporated to determine the material attributes and the critical quality attributes (CQAs). Box behnken design was applied to study the effect of three independent variables X1: amount of lufiflash, X2: amount of pearlitol flash and X3: % of kyron T314 on two responses, Y1: dissolution after 1 minute and Y2: disintegration time. All formulated ODTs showed disintegration time less than 35 seconds and all formulations showed a notable increase in dissolution rate. Design space was determined from the overlay plot of different variables, X1 and X2 and X3 at two levels of the superdisintegrant. The one with maximum predicted dissolution rate and minimum predicted disintegration time was a formulation containing ludiflash (X1)= 9.25 mg, pearlitol flash (X2= 50 mg) and kyron T314= 3%. This formulation (Test ODT) was prepared and was subjected to in vivo study. Mirtazapine in human plasma was determined by LC-MS/MS and different pharmacokinetic parameters was determined for both test ODT and conventional oral tablet (Remeron). The pharmacokinetic parameters indicated that the two formulations are bioequivalence

Site-selectivite Synthesis and Tautomerism of Arylazo Derivatives of Pyrazolo[3,4-d]pyrimido-[1,6-b][1,2,4]triazine

A simple synthetic strategy is described for synthesis of the hitherto unreported 5-arylazo-1,3-diphenyl-6-substituted-1H-pyrazolo[3,4-d]pyrimido[1,6-b][1,2,4]triazines 5a-n. The spectral data indicated that the studied compounds exist predominantly in the hydrazone tautomeric form 5A. The site-selectivity and mechanism of the studied reactions are discussed

Serum vitamin D and IgE levels in infants and children under 2 years of age with recurrent chest wheeze

Background: Wheezing is a very common complaint on admission to the pediatric emergency department. There is an increasing awareness of the important role of vitamin D (VD) in the maintenance of the immune system, recurrent wheezing and respiratory health. Objective: The study aimed to estimate serum 25 hydroxy vitamin D (25OHD), IgE levels and blood eosinophilic count in infants and children under 2 years of age with recurrent wheeze. Methods: This case-control study was carried out on 85 infants (58 males and 27 females; as the patients’ group, ranging in age from 6-24 months, diagnosed to have recurrent wheeze (>3 attacks), recruited from the Pediatric Emergency Department in comparison to 85 age and gender matched healthy infants with no history of wheeze (as the control group). Blood samples were taken from both groups to determine serum 25OHD level, IgE level, and eosinophil count. Results: Serum 25OHD levels of patients were significantly lower than those of controls (p = 0.001), whereas serum IgE and eosinophil counts of patients were significantly higher than those of controls (p <0.0001 for both). Serum levels of 25OHD correlated negatively with the number of wheeze attacks and hospitalization. Conclusion: The study findings revealed lower serum 25OHD levels in infants with recurrent wheeze and provides additional evidence supporting the hypothesis that VD has a role in infant wheeze. VD supplementation might be practical and favorable for better control of recurrent infant wheeze.Keywords:Vitamin D, IgE, Infants, Wheeze

Married adolescent girls in rural Assiut and Souhag: Limited choices and unfulfilled reproductive health needs

According to the Survey of Young People in Egypt 2014, a significant proportion of young women residing in rural Upper Egypt were reported to be married before 18. Early marriage deprives a girl of education and employment opportunities and places her at risk of early and repeat pregnancy, gender-based violence, and sexually transmitted infections. The present study examines the sexual and reproductive health needs of married adolescent girls (MAGs) in rural Upper Egypt and identifies key contextual and cognitive factors that could mitigate or exacerbate the effects of early marriage on their sexual and reproductive health. The report finds that MAGs in rural Assiut and Souhag are experiencing multiple social, economic, and health vulnerabilities. However, despite their dire situation, there are several windows of opportunity that could be capitalized on. The report includes a list of policy and program recommendations that could empower MAGs, address their health needs, and ultimately eliminate child marriage

Novel spectrophotometric method for determination of cinacalcet hydrochloride in its tablets via derivatization with 1,2-naphthoquinone-4-sulphonate

This study represents the first report on the development of a novel spectrophotometric method for determination of cinacalcet hydrochloride (CIN) in its tablet dosage forms. Studies were carried out to investigate the reaction between CIN and 1,2-naphthoquinone-4-sulphonate (NQS) reagent. In alkaline medium (pH 8.5), an orange red-colored product exhibiting maximum absorption peak (λmax) at 490 nm was produced. The stoichiometry and kinetic of the reaction were investigated and the reaction mechanism was postulated. This color-developing reaction was employed in the development of a simple and rapid visible-spectrophotometric method for determination of CIN in its tablets. Under the optimized reaction conditions, Beer's law correlating the absorbance with CIN concentration was obeyed in the range of 3 - 100 μg/ml with good correlation coefficient (0.9993). The molar absorptivity (ε) was 4.2 × 105 l/mol/cm. The limits of detection and quantification were 1.9 and 5.7 μg/ml, respectively. The precision of the method was satisfactory; the values of relative standard deviations (RSD) did not exceed 2%. No interference was observed from the excipients that are present in the tablets. The proposed method was applied successfully for the determination of CIN in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 100.80 - 102.23 ± 1.27 - 1.62%. The results were compared favorably with those of a reference pre-validated method. The method is practical and valuable in terms of its routine application in quality control laboratories

Role of Procalcitonin As an Inflammatory Marker in a Sample of Egyptian Children with Simple Obesity

BACKGROUND: Obesity is a multifactorial disease, associated with metabolic disorders and chronic low-grade inflammation. Procalcitonin (PCT) is well known as a biomarker of infection, and systemic inflammation. Recently, it has potential as a marker for chronic low-grade inflammation.AIM: This study aims to evaluate the role of serum PCT as an inflammatory biomarker in the diagnosis of obesity-related low-grade inflammation.METHOD: In this case-control study, 50 obese and 35 normal weight children and adolescents aged 5–15 years were enrolled. Anthropometric parameters were measured in all subjects. Blood samples were collected for measurement of lipid profile, blood glucose, insulin, high sensitivity-CRP (Hs-CRP) and serum procalcitonin. Serum (PCT) levels were assessed using enzyme-linked immunosorbent assay.RESULTS: Obese participants had higher concentrations of serum PCT, total cholesterol, triglycerides, LDL-c, glucose and Hs-CRP than control group. On correlation analysis, procalcitonin had significant positive correlation with (BMI) z-score (P = 0.02), insulin (P = 0.00), insulin resistance (HOMA-IR) (P = 0.006), Hs-CRP (P = 0.02), total cholesterol (P = 0.04) and triglycerides (P = 0.00) in obese group.CONCLUSION: The increased serum procalcitonin concentrations were closely related to measures of adiposity, Hs-CRP and insulin resistance, suggesting that PCT may be an excellent biomarker for obesity-related chronic low-grade inflammation in children and adolescents

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030