Retraction: A Giant Porencephaly: A Rare Etiology of Pediatric Seizures.

[This retracts the article DOI: 10.7759/cureus.19623.].

Modelling COVID-19 vaccination status and adherence to public health and social measures, Eastern Mediterranean Region and Algeria.

Objective: To study the link between coronavirus disease 2019 (COVID-19) vaccination status and adherence to public health and social measures in Members of the Eastern Mediterranean Region and Algeria. Methods: We analysed two rounds of a large, cross-country, repeated cross-sectional mobile phone survey in June-July 2021 and October-November 2021. The rounds included 14 287 and 14 131 respondents, respectively, from 23 countries and territories. Questions covered knowledge, attitudes and practices around COVID-19, and demographic, employment, health and vaccination status. We used logit modelling to analyse the link between self-reported vaccination status and individuals' practice of mask wearing, physical distancing and handwashing. We used propensity score matching as a robustness check. Findings: Overall, vaccinated respondents (8766 respondents in round 2) were significantly more likely to adhere to preventive measures than those who were unvaccinated (5297 respondents in round 2). Odds ratios were 1.5 (95% confidence interval, CI: 1.3-1.8) for mask wearing; 1.5 (95% CI: 1.3-1.7) for physical distancing; and 1.2 (95% CI: 1.0-1.4) for handwashing. Similar results were found on analysing subsamples of low- and middle-income countries. However, in high-income countries, where vaccination coverage is high, there was no significant link between vaccination and preventive practices. The association between vaccination status and adherence to public health advice was sustained over time, even though self-reported vaccination coverage tripled over 5 months (19.4% to 62.3%; weighted percentages). Conclusion: Individuals vaccinated against COVID-19 maintained their adherence to preventive health measures. Nevertheless, reinforcement of public health messages is important for the public's continued compliance with preventive measures.

Patellofemoral contact forces and knee gait mechanics 3 months after ACL reconstruction are associated with cartilage degradation 24 months after surgery.

OBJECTIVE: Evaluate patellofemoral cartilage health, as assessed by quantitative magnetic resonance imaging (qMRI) T2 relaxation times, 24-months after ACL reconstruction (ACLR) and determine if they were associated with patellofemoral contact forces and knee mechanics during gait 3 months after surgery. DESIGN: Thirty individuals completed motion analysis during overground walking at a self-selected speed 3 months after ACLR. An EMG-driven neuromusculoskeletal model was used to determine muscle forces, which were then used in a previously described model to estimate patellofemoral contact forces. Biomechanical variables of interest included peak patellofemoral contact force, peak knee flexion angle and moment, and walking speed. These same participants underwent a sagittal bilateral T2 mapping qMRI scan 24-months after surgery. T2 relaxation times were estimated for both patellar and trochlear cartilage. Paired t-tests were used to compare T2 relaxation times between limbs while Pearson correlations and linear regressions were utilized to assess the association between the biomechanical variables of interest and T2 relaxation times. RESULTS: Prolonged involved limb trochlear T2 relaxation times (vs uninvolved) were present 24-months after surgery, indicating worse cartilage health. No differences were detected in patellar cartilage. Significant negative associations were present within the involved limb for all the biomechanical variables of interest 3 months after ACLR and trochlear T2 relaxation times at 24-months. No associations were found in patellar cartilage or within the uninvolved limb. CONCLUSIONS: Altered involved limb trochlear cartilage health is present 24-months after ACLR and may be related to patellofemoral loading and other walking gait mechanics 3 months after surgery.

Modelling COVID-19 vaccination status and adherence to public health and social measures, Eastern Mediterranean Region and Algeria

Objective: To study the link between coronavirus disease 2019 (COVID-19) vaccination status and adherence to public health and social measures in Members of the Eastern Mediterranean Region and Algeria. Methods: We analysed two rounds of a large, cross-country, repeated cross-sectional mobile phone survey in June­July 2021 and October­November 2021. The rounds included 14 287 and 14 131 respondents, respectively, from 23 countries and territories. Questions covered knowledge, attitudes and practices around COVID-19, and demographic, employment, health and vaccination status. We used logit modelling to analyse the link between self-reported vaccination status and individuals' practice of mask wearing, physical distancing and handwashing. We used propensity score matching as a robustness check. Findings: Overall, vaccinated respondents (8766 respondents in round 2) were significantly more likely to adhere to preventive measures than those who were unvaccinated (5297 respondents in round 2). Odds ratios were 1.5 (95% confidence interval, CI: 1.3­1.8) for mask wearing; 1.5 (95% CI: 1.3­1.7) for physical distancing; and 1.2 (95% CI: 1.0­1.4) for handwashing. Similar results were found on analysing subsamples of low- and middle-income countries. However, in high-income countries, where vaccination coverage is high, there was no significant link between vaccination and preventive practices. The association between vaccination status and adherence to public health advice was sustained over time, even though self-reported vaccination coverage tripled over 5 months (19.4% to 62.3%; weighted percentages). Conclusion Individuals vaccinated against COVID-19 maintained their adherence to preventive health measures. Nevertheless, reinforcement of public health messages is important for the public's continued compliance with preventive measures.

Microscopic Evaluation of Ovarian Surface Epithelium Following Treatment with Conjugated Estrogens in a Mouse Model.

BACKGROUND: This study was designed to evaluate the effect of different concentrations of conjugated equine estrogens (CEE) on the ovarian epithelium of female CD1 mice. METHODS: Twenty-four female mice at 7 months with irregular estrus cycles were randomly divided into four groups of 6 mice each. Group one was considered as a control group and received a daily dose of 0.5ml of propylene glycol, for three weeks, while those in the treatment groups received a daily dose of 14µg/kg, 28µg/kg and 56µg/kg conjugated equine estrogens, respectively. RESULTS: The results from this study showed a strong correlation between elevated concentrations of CEE and histological changes in ovarian surface epithelium (OSE). They also showed that administration of high-dose estrogen created the conditions for excessive proliferation of OSE which may progress into the development of cysts in the ovaries. CONCLUSION: This study concluded that high concentrations of CEE may increase the chances of developing epithelial ovarian cancer.

Public health emergency operation centres: status, gaps and areas for improvement in the Eastern Mediterranean Region.

The functionality of Public Health Emergency Operations Centres (PHEOCs) in countries is vital to their response capacity. The article assesses the status of National PHEOCs in the 22 countries of the Eastern Mediterranean Region. We designed and administered an online survey between May and June 2021. Meetings and Key Informant Interviews were also conducted with the emergency focal points in the WHO country offices and with other select partners. We also collected data on PHEOCs from the Joint External Evaluations conducted in the Region between 2016 and 2018 in 18 countries, and intra-action review mission reports conducted in 11 countries to review the response to COVID-19 during May 2020-June 2021 - and other relevant mission reports. Only 12 countries reported having PHEOC with varying levels of functionality and 10 of them reported using PHEOC for their response operations. This review formed the baseline of capacity requirements of National PHEOC in each country and will facilitate identifying benchmarks of areas of improvement for future national, WHO and partners support.

Randomized controlled trial of colchicine add on to the standard therapy in moderate and severe corona virus Disease-19 infection.

Background: COVID19 complications cause inflammatory storm. Colchicine is a potent anti-inflammatory medication that has been proposed as a possible treatment option for COVID-19. Objective: to assess effectiveness and safety of add on use of colchicine to the standard treatment in moderate and severe COVID-19. Patients and methods: In this randomized controlled open label clinical trial, 160 patients hospitalized equally divided between moderate and severe COVID19 categories were randomized to 4 study groups in a 1:1:1:1 allocation (n = 40 for each group) according to type of treatment. Patients were randomly assigned to receive the standard treatment for 14 days (control group) or colchicine add on to the standard treatment 1 mg daily orally for 7 days then 0.5 mg daily for another 7 days. Survival rate, time to cure in days, and side effects were assessed. Results: Colchicine add on treatment was associated with a significantly shorter time to cure (referring to start of first symptom) by an average of 5 days in severe disease and 2 days in moderate disease (log-rank P=<0.001). In addition, the Colchicine add on significantly increased the risk of cure per unit of time by 2.69 times compared to controls after adjusting for disease severity, age, and time since the start of the disease to start of treatment. A severe COVID19 disease, a longer time for starting treatment, and the older age notably reduced the risk of cure (HR = 0.72, p = 0.07; HR = 0.74, p < 0.001; and HR = 0.59, p = 0.015 respectively). Possible side effects reported due to colchicine were 8/40 (20%) of severe COVID19 patients and 3/40 (7.5%) of moderate COVID19, non of which warranted stopping treatment by the data monitoring board. Generally, the side effects were 8/11 (72.73%) gastrointestinal disturbances. No immediate or late allergic reactions were observed. Conclusions: Colchicine add on treatment reduced significantly time to recovery in severe COVID19 (by five days) and in moderate cases (by two days) but did not lower the death rate. Side effects were mild, well tolerated and confined to gastrointestinal adverse events.

Optimized Nanoparticles for Enhanced Oral Bioavailability of a Poorly Soluble Drug: Solid Lipid Nanoparticles Versus Nanostructured Lipid Carriers.

INTRODUCTION: Rosuvastatin calcium (ROSCa) is an anti-hyperlipidemic drug with only 20% oral bioavailability due to its low solubility and high first-pass metabolism. Therefore, the main purpose of this work was to compare solid lipid nanoparticles to nanostructured lipid carriers and evaluate their effect on solubility improvement and hence the bioavailability of a model insoluble drug. METHODS: Different nanosuspensions were formulated using high-speed homogenization and ultrasonication techniques, using Apifil as solid lipid and Maisine as liquid lipid. The effect of different variables on quality attributes (particle size, entrapment efficiency (EE), and in vitro release) was studied using the Box-Behnken design. Then, the optimized nanoparticles were lyophilized, filled into capsules, and evaluated. Finally, the optimized formula was clinically evaluated in six healthy human volunteers. RESULTS: It was observed that the variables had a great impact on EE and particle size. Nanoparticles showed maximum particles of 180.3 nm, and % EE ranged from 40.77% to 91.67%. Capsules loaded with NLCs were found to be more stable than those loaded with SLNs. The clinical study of NLCs-ROSCa showed an enhancement in the C max (8.92 ng/ml) compared to the commercial product (2.56 ng/ml) with approximately 349% relative bioavailability. CONCLUSION: ROSCa was successfully encapsulated in SLNs and NLCs. The optimized NLCs formulation showed improved quality attributes compared to SLNs. Thus, NLCs loaded formulations could be an effective oral drug delivery system to enhance the bioavailability of insoluble drugs.

Conflict-related health research in Syria, 2011-2019: a scoping review for The Lancet - AUB Commission on Syria.

BACKGROUND: The volume of health-related publications on Syria has increased considerably over the course of the conflict compared with the pre-war period. This increase is largely attributed to commentaries, news reports and editorials rather than research publications. This paper seeks to characterise the conflict-related population and humanitarian health and health systems research focused inside Syria and published over the course of the Syrian conflict. METHODS: As part of a broader scoping review covering English, Arabic and French literature on health and Syria published from 01 January 2011 to 31 December 2019 and indexed in seven citation databases (PubMed, Medline (OVID), CINAHL Complete, Global Health, EMBASE, Web of Science, Scopus), we analyzed conflict-related research papers focused on health issues inside Syria and on Syrians or residents of Syria. We classified research articles based on the major thematic areas studied. We abstracted bibliometric information, study characteristics, research focus, funding statements and key limitations and challenges of conducting research as described by the study authors. To gain additional insights, we examined, separately, non-research publications reporting field and operational activities as well as personal reflections and narrative accounts of first-hand experiences inside Syria. RESULTS: Of 2073 papers identified in the scoping review, 710 (34%) exclusively focus on health issues of Syrians or residents inside Syria, of which 350 (49%) are conflict-related, including 89 (25%) research papers. Annual volume of research increased over time, from one publication in 2013 to 26 publications in 2018 and 29 in 2019. Damascus was the most frequently studied governorate (n = 33), followed by Aleppo (n = 25). Papers used a wide range of research methodologies, predominantly quantitative (n = 68). The country of institutional affiliation(s) of first and last authors are predominantly Syria (n = 30, 21 respectively), the United States (n = 25, 19 respectively) or the United Kingdom (n = 12, 10 respectively). The majority of authors had academic institutional affiliations. The most frequently examined themes were health status, the health system and humanitarian assistance, response or needs (n = 38, 34, 26 respectively). Authors described a range of contextual, methodological and administrative challenges in conducting research on health inside Syria. Thirty-one publications presented field and operational activities and eight publications were reflections or first-hand personal accounts of experiences inside Syria. CONCLUSIONS: Despite a growing volume of research publications examining population and humanitarian health and health systems issues inside conflict-ravaged Syria, there are considerable geographic and thematic gaps, including limited research on several key pillars of the health system such as governance, financing and medical products; issues such as injury epidemiology and non-communicable disease burden; the situation in the north-east and south of Syria; and besieged areas and populations. Recognising the myriad of complexities of researching active conflict settings, it is essential that research in/on Syria continues, in order to build the evidence base, understand critical health issues, identify knowledge gaps and inform the research agenda to address the needs of the people of Syria following a decade of conflict.

A Giant Porencephaly: A Rare Etiology of Pediatric Seizures.

Pediatric convulsive seizure is common and represents a source of major concern and anxiety for the parents. Seizures can have a broad spectrum of etiologies in children, including metabolic, traumatic, developmental, and infectious causes. Depending on the clinical presentation, laboratory testing and neuroimaging may be indicated in the workup of the first unprovoked afebrile seizure. We present a case of a six-year-old boy who was brought to the emergency department by his mother after an episode of convulsion. She reported that he had jerky repetitive movements of all extremities that lasted around two minutes with spontaneous termination. The child did not have a febrile illness. The mother reported no history of similar episodes. Upon examination, the child appeared alert and conscious. No dysmorphic features were evident. Initial laboratory investigations were within the normal limits. The child underwent magnetic resonance imaging for the brain, which demonstrated a large well-defined extra-axial cystic lesion occupying most of the left hemisphere that is connected to the ventricular system. The lesion had no grey-matter lining and it strictly followed the cerebrospinal fluid in all sequences. Such finding represented the diagnosis of a giant left porencephalic cyst. Porencephaly is an extremely rare neurological anomaly that may present with pediatric seizures. Magnetic resonance imaging is the gold standard modality for the diagnosis of porencephaly. The case demonstrated that porencephaly can have a massive size in a patient with normal psychoneurological development.

A randomised controlled trial of effectiveness and safety of Niclosamide as add on therapy to the standard of care measures in COVID-19 management.

BACKGROUND: COVID-19 pandemic has ignited the urge for repurposing old drugs as candidate antiviral medicines to treat novel challenges of viral infections. Niclosamide (NCS) is an anti-parasitic drug of known antiviral potential. Therefore, this study attempts to investigate the antiviral effect and safety of NCS on SARS-CoV-2 caused COVID-19 patients. METHODS: Randomized controlled open label clinical trial encompassed 75 COVID-19 patients treated with standard of care plus NCS were included as experimental group and 75 COVID-19 patients treated with only standard of care therapy as control group. Survival rate, time to recovery, and side effects were the main endpoints for the assessment of the therapeutic effect and safety of NCS. RESULTS: No significant difference between the two study groups in the incidence of death Vs recovery within 30 days of follow up(p = 1).Median survival time to cure in the NCS addon group was significantly less than controls (5 Vs 7days, Log rank p = 0.005).All the recoveries took place within 20 days in the NCS add on group, which is 10 days shorter than that in the controls (30 days), NCS add on treatment increased the risk of cure by 60% per day compared to control group (adjusted HR = 1.6,p = 0,007) after adjusting for the count of comorbidities. Additionally, two or more comorbidities reduced the risk of cure to 33% (p < 0.001).Male gender increased the risk of cure by 42% (p = 0.046). Older age group decreased the risk of recovery per day to 0.58 and 0.53 for 50-59 and 60+ years of age. Hyypertension (HT) and diabetes mellitus (DM) significantly reduced the risk of being cured per day to 0.56 (p = 0.003)and 0.65 (p = 0.039) respectively. No significant signals of safety in NCS add on therapy compared to control group. CONCLUSION: adding NCS to the standards of care measures increased the risk of the cure and had shorter time to stay in the hospital compared with controls., male gender increased the risk of cure, while older patients>40 years, HT, and DM decreased the risk of cure. Also, NCS add on therapy was relatively safe; hence, NCS is of clinical benefit for freeing hospital beds for more patients in pandemic crisis.

Early Nutrition with Different Diets Composition versus Fasting on Immunity-Related Gene Expression and Histomorphology of Digestive and Lymphoid Organs of Layer-Type Chicks.

Early feeding post-hatching (EFPH) can impact the immune response and modify the immunity-related gene expression. Therefore, we aimed to examine the effects of EFPH with different diets composition versus fasting during the first 72 h of chick's life on the histomorphological structures of the liver, proventriculus, central and peripheral lymphoid organs, and immunity-related genes in layer-type chicks during the brooding period. A total of 400 chicks were randomly allotted into 4 groups with 4 replicates each. The experimental groups during the first 72 h of life were: feed and water deprivation (control, T1), feeding a starter layer diet (20% CP and 11.84 MJ/kg ME, T2), feeding a starter layer diet contained 3% molasses in its composition (20% CP and 11.81 MJ/kg ME; T3), and feeding a starter broiler diet (23% CP and 12.68 MJ/kg ME, T4). After the first 72 h of chick's life, all chicks were fed ad libitum the T2 diet. EFPH had no negative effect on the development of the lymphoid or digestive organs in chicks. Greater relative weights of the spleen and bursa of Fabricius (p < 0.05) were observed in the early fed chicks compared to control at day 14 of age. Histomorphological examination revealed an increase (p < 0.05) in thymus cortex and cortex:medulla in the T3 and T4 groups compared to the fasted ones at day 28 of age. Pelicae height, follicular width, cortex, and cortex:medulla of bursa were improved (p < 0.01) in the fed groups compared to fasted chicks, with resultant influences on the primary lymphoid organs. Compared to control, higher germinal center areas and white pulp of the spleen (p < 0.05) were recorded in the early fed chicks, implying augmented proliferation and maturation of B cells in the secondary lymphoid organs. In the liver, a strong positive reaction to Best's carmine stain in the early fed groups, indicating that the liver of these chicks had numerous glycogen granules or greater glycogen density in the cytoplasm of hepatocytes. There was a significant enhancement in the proventriculus mucosal and gland thickness, as well as fold height (p < 0.05) in the early fed chicks. The expression levels of splenic Toll-like receptor 2, interleukin 4, tumor necrosis factor α, and interferon gamma were up-regulated (p < 0.01) in most of the early fed chicks (T2, T3, and T4) compared to fasted ones at 14 day of age. In conclusion, EFPH could modify the splenic-immunity related genes and modulate the histomorphology of the digestive (liver and proventriculus) and lymphoid organs in layer-type chicks during the brooding period.

Effectiveness and Safety of Niclosamaide as Add-on Therapy to the Standard of Care Measures in COVID-19 Management: Randomized controlled clinical trial

BackgroundCOVID-19 pandemic has ignited the urge for repurposing old drugs as candidate antiviral medicines to treat novel challenges of viral infections. Niclosamide (NCS) is an anti-parasitic drug of known antiviral potential. Therefore, this study attempts to investigate the antiviral effect and safety of NCS on SARS-CoV-2 caused COVID-19 patients. MethodsRandomized controlled open label clinical trial encompassed 75 COVID-19 patients treated with standard of care plus NCS were included as experimental group and 75 COVID-19 patients treated with only standard of care therapy as control group. Each group was composed of 25 mild, 25 moderate and 25 severe patients. Survival rate, time to recovery, and side effects were the main endpoints for the assessment of the therapeutic effect and safety of NCS. ResultsNCS did not enhance survival rate as three of severe COVID-19 patients in NCS and in control groups died (P>0.05). However, NCS, compared to control group, reduced the time to recovery in moderate and severe COVID-19 patients about 5 and 3 days, respectively but not in mild patients (P[≤]0.05). Most interestingly, NCS lowered time to recovery up to five days in patients with co-morbidities (P[≤]0.05) whereas only one day lowered in patients without co-morbidities (P>0.05). ConclusionIt is concluded that NCS accelerates time to recovery about 3 to 5 days in moderate to severe COVID-19 patients especially those with co-morbidities; hence, NCS is of clinical benefit for freeing hospital beds for more patients in pandemic crisis.

Health-related articles on Syria before and after the start of armed conflict: a scoping review for The Lancet-American University of Beirut Commission on Syria.

INTRODUCTION: Armed conflict may influence the size and scope of research in Arab countries. We aimed to assess the impact of the 2011 Syrian conflict on health articles about Syria published in indexed journals. METHODS: We conducted a scoping review on Syrian health-related articles using seven electronic databases. We included clinical, biomedical, public health, or health system topics published between 1991 and 2017. We excluded animal studies and studies conducted on Syrian refugees. We used descriptive and social network analyses to assess the differences in rates, types, topics of articles, and authorship before and after 2011, the start of the Syrian conflict. RESULTS: Of 1138 articles, 826 (72.6%) were published after 2011. Articles published after 2011 were less likely to be primary research; had a greater proportion reporting on mental health (4.6% vs. 10.0%), accidents and injuries (2.3% vs. 18.8%), and conflict and health (1.7% vs. 7.8%) (all p < 0.05); and a lower proportion reporting on child and maternal health (8.1 to 3.6%, p = 0.019). The proportion of research articles reporting no funding increased from 1.1 to 14.6% (p < 0.01). While international collaborations increased over time, the number of articles with no authors affiliated to Syrian institutions overtook those with at least one author affiliation to a Syrian institution for the first time in 2015. CONCLUSION: To our knowledge, this is the first study to examine the impact of armed conflict on health scholarship in Syria. The Syrian conflict was associated with a change in the rates, types, and topics of the health-related articles, and authors' affiliations. Our findings have implications for the prioritization of research funding, development of inclusive research collaborations, and promoting the ethics of conducting research in complex humanitarian settings.

Preparation of biocompatible chitosan nanoparticles loaded by tetracycline, gentamycin and ciprofloxacin as novel drug delivery system for improvement the antibacterial properties of cellulose based fabrics.

The main aim of this research work was to develop controlled drug delivery systems based on nanotechnology. Chitosan nanoparticles (CSNPs) were selected as a nanocarrier for the selected antibiotic drugs tetracycline, gentamycin and ciprofloxacin. CSNPs were prepared from chitosan solution by using tripolyphosphate (TPP) via ionic gelation method. Then the prepared high performance CSNPs were loaded with three different antibiotics to form nanocomposite from antibiotic loaded chitosan nanoparticles. Then the prepared nanocomposite used as superior antibacterial materials with minimum toxicity. Samples of cotton (100%) and (50:50) cotton/polyester blended fabrics were treated with different concentrations of this composite to impart antibacterial activity. Results showed that the treated fabrics with chitosan nanoparticles and its nanocomposite with different antibiotics were inhibited the growth of both Gram-positive and Gram-negative bacteria. The Fourier Transform Infrared spectroscopy (FTIR) and Scanning Electron Microscope (SEM) analysis exposed the embedding of chitosan nanoparticles into fabrics and their antibiotics loaded.

Validation of the modified NUTRIC score on critically ill Jordanian patients: A retrospective study.

BACKGROUND: Nutritional status has been proven to be associated with poor outcomes in mechanically ventilated patients in intensive care units (ICU). Nutritional assessment has been assessed using different tools. Few data are available on the validity of the modified Nutrition Risk Assessment Tool for Critically Ill (mNUTRIC) score in ICU patients receiving mechanical ventilation (MV). AIM: This study aimed to assess prognostic performance of the mNUTRIC score for discriminative abilities for 30-day mortality and prolonged MV. METHODS: This was a multi-centre retrospective study that included 737 mechanically ventilated patients using secondary data analysis. Data were collected on variables required to calculate mNUTRIC score. Patients with a mNUTRIC score ≥5 were considered at nutritional risk. Predictive performance of the mNUTRIC was assessed for discriminative abilities for Acute Physiology and Chronic Health Evaluation II at baseline, mortality in 42 days of follow-up and outcomes related to MV. RESULTS: A total of 737 patients on MV met the inclusion criteria. The majority (57.1%) of patients were male. The mean age of the participants was 62.1±18 years. Of all patients, 482 (58%) were at high nutritional risk (mNUTRIC score ≥5). Median ventilator days were 3 (±7.2) days and 72 (±174) hours. The overall mortality rate was 78.8% (n=652), and weaning failure was 79.8% (n=660). CONCLUSIONS: This study showed new evidence on the validity of the mNUTRIC as a tool for assessing nutritional risk in an ICU population in Jordan. The mNUTRIC score obtained from the current retrospective data suggests that the use of the tool can truly identify and diagnose critically ill patients with malnutrition.

Development of medicated chewing gum of taste masked levocetirizine dihydrochloride using different gum bases: in vitro and in vivo evaluation.

Objective: The aim of this study was to develop medicated chewing gum (MCG) formulation for taste-masked levocetirizine dihydrochloride (LCZ) that can provide fast drug release into the salivary fluid.Methods: Taste-masked LCZ was first prepared by two methods: cyclodextrin complexation using Kleptose or Captisol and formation of drug resin complex using Kyron T-154 or Kyron T-314 to overcome poor LCZ palatability. MCGs were then prepared using the taste-masked drug, gum base (Artica-T, Chicle, or Health In Gum (HIG), plasticizer (glycerol or soy lecithin at 6 or 8% of the final gum weight). The developed MCGs were evaluated for physical properties, content uniformity, and drug release. Best release MCGs were evaluated thermally to investigate the plasticizer effectiveness and for ex vivo chew out study to confirm adequate drug release. Drug bioavailability was determined for selected formula compared to commercial tablets.Results: Based on taste-masking efficiency, drug/Kleptose complex (1:3 molar ratio) was chosen for incorporation into chewing gums. Physical properties and drug release showed that gum base type, plasticizer type, and level affected not only physical properties but also drug release from MCGs. Thermal study showed decreased glass transition temperature (Tg) with increased plasticizer level. Chew out study confirmed almost complete drug release after a few minutes of chewing. Pharmacokinetic results showed shorter tmax (0.585 vs. 1.375 h) and higher Cmax (0.113 vs. 0.0765 µg/mL) for MCGs than conventional tablets.Conclusion: Results provided evidence that MCGs could be a better alternative to conventional tablet formulations with improved bioavailability and enhanced palatability.

Formulation, optimization, and evaluation of raft-forming formulations containing Nizatidine.

OBJECTIVE: The main objective of this research is to formulate, optimize, and evaluate raft-forming chewable tablets of Nizatidine. Various raft-forming agents were used in preliminary screening. Sodium alginate showed maximum raft strength, so tablets were prepared using sodium alginate as the raft forming agent, along with calcium carbonate (CaCO3) as antacid and raft strengthening agent, and sodium bicarbonate (NaHCO3) as a gas generating agent. RESEARCH DESIGN AND METHODS: Raft forming chewable tablets containing Nizatidine were prepared by direct compression and wet granulation methods, and evaluated for drug content, acid neutralization capacity, raft strength, and in-vitro drug release in 0.1 N HCl. Box-Behnken design was used for optimization. RESULTS: Two optimized formulations were predicted from the design space. The first optimized recommended concentrations of the independent variables were predicted to be X1 = 275.92 mg, X2 = 28.60 mg, and X3 = 202.14 mg for direct compression technique and the second optimized recommended concentrations were predicted to be X1 = 253.62 mg, X2 = 24.60 mg, and X3 = 201.77 mg for wet granulation technique. Optimized formulations were stable at accelerated environmental testing for six months at 35 °C and 45 °C with 75% relative humidity. X-Ray showed that the raft floated immediately after ingestion and remained intact for ∼3 h. CONCLUSION: Raft was successfully formed and optimized. Upon chewing tablets, a raft is formed on stomach content. That results in rapid relief of acid burning symptoms and delivering the drug into systemic circulation with enhanced bioavailability.