FORMULATION AND EVALUATION OF TRANSDERMAL PATCHES OF METOPROLOL TARTRATE USING PERMEATION ENHANCERS OF NATURAL AND SYNTHETIC ORIGIN

Objective: Oral metoprolol tartrate has a short elimination half-life (2-3h) and low bioavailability undergoes extensive first-pass metabolism and frequent dosing. The aim of the present investigation was to formulate, develop and evaluate metoprolol tartrate transdermal patches using various synthetic and natural penetration enhancers. Methods: Enhancers used were eugenol, limonene, basil oil, urea and SLS (sodium lauryl sulphate). Polymer used was chitosan and PEG 400 used as a plasticizer. Transdermal Films were prepared by using solvent casting method. FTIR and DSC were studied to assess any interaction between the drug and polymers. Films were evaluated for Physico-chemical Characteristics like thickness, weight variation, folding endurance, moisture loss, moisture absorption and drug content. In vitro skin permeation studies were performed using Keshary chien cell For 24 h across rat skin. Results: Chitosan was found to be a suitable polymer for matrix formation. 3.5% w/w was used to optimize to formulate transdermal patches. 1.5% of total solution v/v lactic acid was used for dissolution of chitosan. 2.5%v/v of total solution PEG 400 was used to provide plasticity and smoothness to the patches. From the evaluation of patches formulation, F10 containing Basil oil as penetration enhancer in the concentration of 1.5% v/v was found to be best among all batches because of its consistent release rate For 24 h and extent of drug release was 85.20%. It can be concluded that naturally occurring volatile oils i.e., terpenes appear acceptable permeation enhancer and shows the best permeation across skin as indicated by high percutaneous enhancement ability. Conclusion: The developed transdermal patches are stable, non-irritating, and had increased efficacy of metoprolol and therefore had a good potential for hypertension treatment

FORMULATION AND DEVELOPMENT OF TRANSDERMAL DRUG DELIVERY SYSTEM OF ETHINYLESTRADIOL AND TESTOSTERONE: IN VITRO EVALUATION

Objective: The combination therapy of ethinylestradiol and testosterone in post-menopausal females has shown improved sexual response and libido. The present studies were designed to develop a suitable matrix-type transdermal drug delivery system (TDDS) of ethinylestradiol and testosterone using the polymer chitosan.Methods: Five formulations (ET1 to ET5) were developed by varying the concentration of polymer and keeping the drug load constant. Physical parameters and drug excipient interaction studies were evaluated in all the formulations. In vitro skin permeation profiles of ethinylestradiol and testosterone from various formulations were simultaneously characterized in a thermostatically controlled modified Franz Diffusion cell using HPLC. Based on the physical parameters and in vitro skin permeation profile formulation ET3 containing 30 mg/ml of chitosan was found to be the best and chosen for further studies. Optimized formulation was subjected to in vivo pharmacokinetic analysis in rats using ELISA.Results: Stability profile of patch formulation ET3 depicted stability up to 3 mo. One week skin irritation evaluation in rats indicated that formulation ET3 was nonirritating. Combination transdermal patch across rat skin showed a maximum release of 92.936 and 95.03 % in 60 h with a flux of 2.088 and 21.398 µg/cm2h for ethinylestradiol and testosterone respectively.Conclusion: The net result of this study is the formulation of a stable, non-irritating transdermal patch of ethinylestradiol and testosterone, with good bioavailability and can be used as Estrogen Replacement Therapy (ERT) in postmenopausal women

FORMULATION DEVELOPMENT AND EVALUATION OF PRONIOSOMAL GEL OF ETHINYLESTRADIOL AND LEVONORGESTREL FOR ANTIFERTILITY TREATMENT

Objective: The purpose of this research was to develop and formulate proniosomal gel drug delivery system of ethinylestradiol and levonorgestrel for antifertility treatment that is capable of efficiently delivering entrapped drug over an extended period of time.Methods: Ethinylestradiol and levonorgestrel are encapsulated in various formulations of proniosomal gel composed of various ratios of span surfactant, cholesterol, soya lecithin, and alcohol as aqueous phase prepared by coacervation-phase separation method. The prepared formulations characterized for drug encapsulation efficiency, size distribution, in vitro release studies, and vesicular stability at different storage conditions were carried. Stability studies for proniosomal gel were carried out for a few weeks. Morphological size and shape of the vesicles are characterized using optical microscopy and scanning electron microscopy (SEM). Stability studies for proniosomal gel were carried out for 3 months.Results: Morphological size and shape of the vesicles are characterized using optical microscopy and SEM, particles are found to be spherical, size of the particles is in the range of 46.4–80.6 nm, and permeation studies showed good control release for prolonged period of time. The encapsulation efficiency of proniosomal gel formulations is in the range of 74–80% and in vitro permeation studies proved that good amount of drug is permeated and has reasonably good stability characteristics as well.Conclusions: The results suggest that proniosomal gel formulations of ethinylestradiol and levonorgestrel may be used for transdermal delivery for antifertility treatment. The dried proniosomal formulation could act as a promising alternative to niosomes

EFFECT OF HYDROPHILIC AND HYDROPHOBIC POLYMER MATRIX ON THE TRANSDERMAL DRUG DELIVERY OF ETHINYLESTRADIOL AND MEDROXYPROGESTERONE ACETATE

Objective: The aims of the present study were to develop different matrix patches with various ratios of hydrophilic and hydrophobic polymer combinations such as ethyl cellulose (EC) and polyvinylpyrrolidone (PVP) and eudragit RL 100 (ERL) and eudragit RS 100 (ERS) containing ethinylestradiol and medroxyprogesterone acetate and to perform physicochemical characterization and in vitro permeation studies through rat skin.Methods: Six formulations (F1 to F6) were developed by varying the concentration of both hydrophilic and hydrophobic polymer and keeping the drug load constant. Physical parameters and drug excipient interaction studies were evaluated in all the formulations. In vitro, skin permeation profiles of ethinylestradiol and medroxyprogesterone acetate from various formulations were simultaneously characterized in a thermostatically controlled modified Franz Diffusion cell. The physicochemical compatibility of the drug and the polymers was studied by differential scanning calorimetry.Results: The results suggested no physicochemical incompatibility between the drug and the polymers. In vitro permeation studies were performed by using Franz diffusion cells, patches coded as F3 (ethyl cellulose: polyvinylpyrrolidone, 7.5:2.5) and F6 (eudragit RL 100 (ERL) and eudragit RS 100 (ERS), 8:2) can be chosen for further in vivo studies. The results followed Higuchi kinetics (r = 0.9953-0.9979), and the mechanism of release was diffusion mediated. Based on physicochemical and in vitro skin permeation studies of 85.64% (for F3) and 88.62% (for F6) of ethinylestradiol and medroxyprogesterone acetate.Conclusion: The developed transdermal patches are stable, non-irritating and had increased efficacy of ethinylestradiol and medroxyprogesterone acetate and therefore had a good potential for antifertility treatment

Power Rotational Interleaver on an Idma System

In this paper we are proposing an interleaver design i.e. power rotational interleaver. The basic purpose of this design is to reduce the bandwidth occupied by the interleaver. This approach provides an efficient result for multiple users. The complexity of this design is same as that of master random interleaver while the bandwidth requirement is reduced up to a great extent. On the basis of simulation results it is concluded that the performance of power rotational interleaver is as good as that is of random interleaver. Keywords: Master random interleaver, a posteriori probability, tree based interleaver

Maternal and perinatal outcome in eclampsia at a tertiary care center

Background: Preeclampsia is the occurrence of hypertension in combination with proteinuria, developing after 20 weeks gestation in a previously normotensive non-proteinuric patient. The objective of this study was to study the prevalance of eclampsia at PGIMS, Rohtak. To study the clinical profile, maternal and perinatal outcome in eclamptic patients.Methods: This is a retrospective study and case records of all eclampsia cases were analysed from the study period of January 2018 to December 2018.Results: There were 113 cases of eclampsia out of 11,661 deliveries and prevalence of eclampsia was calculated to be 0.96%. Majority of the patients were not registered 95.57%. 58% of patients were Primigravidas. 56% of the patient in the age group of 21-25 years. Antepartum, intrapartum and postpartum eclampsia were 71%, 1.7% and 27% respectively. Caesarean section was the preferred mode of delivery and was performed in 57% cases. ICU admission was required in 25% and remaining cases were managed in general/eclampsia ward. All patients received MgSO4 by Zuspan regimen. 12% patient developed HELLP syndrome and pulmonary oedema developed in 6% patient. There were a total of 3.5% maternal deaths during the study period. Total percentage of perinatal deaths due to eclampsia was 23%.Conclusions: Eclampsia continues to be one of the prime etiological factors for maternal and perinatal morbidity and mortality. This is due to lack of proper antenatal care, low socioeconomic condition and lack of education. Regular antenatal checkup, early recognition and proper management are vital to tackle this challenge. MgSo4 is the anticonvulsant of choice and Zuspan regimen of MgSO4 is effective in the management of eclampsia

Yolk sac tumor in an antenatal patient: a challenging case

Pregnancy complicated with adnexal masses is a very common occurrence. However, most of these adnexal masses encountered in pregnancy are benign in nature and are found incidentally during routine antenatal ultrasound. Malignant ovarian neoplasms account for 1%-8% of all persistent adnexal masses diagnosed during pregnancy. Yolk sac tumor (YST) complicating pregnancy is very rare and has no proper guidelines for its diagnosis and management hence causing a therapeutic dilemma for the clinicians. Therefore, an individualised approach is preferred in such cases. It is very important to report such cases for better understanding and management of these cases. Here we present a case report of a 23-year-old primigravida at 30 weeks gestation with yolk sac tumor of right ovary, surgical stage IIIc who responded well to fertility sparing surgery with cisplatin-based combination chemotherapy. She has no evidence of disease post treatment and has been put on regular follow up

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

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 middle-income 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 low-income 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 low-income, 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

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