MULTIPARTICULATE FLOATING DRUG DELIVERY SYSTEM OF ANAGLIPTIN: DESIGN AND OPTIMIZATION FOR ITS EFFICACY IN MANAGEMENT OF METABOLIC SYNDROME

Objective: The present research aims to design and optimize gastroretentive floating pellets of anagliptin (a dipeptidyl peptidase-4 inhibitor), so as to reduce P-Glycoprotein (PGP)–mediated efflux in the intestine hence to improve oral bioavailability. Methods: The drug-containing core pellets were prepared by extrusion and spheronization process followed by subsequent coating with three successive layers i.e. Eudragit RS 100, sodium bicarbonate (NaHCO3): hydroxypropyl methylcellulose E5LV (HPMC E5LV) and Eudragit RL 100 using fluidized bed processor. A 3 level 3 factor box-behnken design was adopted to investigate the effect of Eudragit RS 100, NaHCO3: HPMC E5LVand Eudragit RL 100 on floating lag time and drug release at 10 h. Desirability function under numerical optimization technique was used to identify the optimum formulation. Results: The study reveals the significant effect of the amount of NaHCO3 and coating level of polymers on floating lag time and drug release. The optimum system could float within 4 min and exhibited more than 85% drug release in 10 h. The pharmacokinetic study conducted in male Wistar rats indicated 2.51 fold increase in relative bioavailability of optimized formulation compare to anagliptin drug. Formulated anagliptin pellets were evaluated in cafeteria diet-induced metabolic syndrome model in male Wistar rats. Anagliptin floating pellets treatment compared to cafeteria diet group significantly inhibited increase in body weight (238.79±2.52 g vs. 277.98±3.69 g, P<0.001), calorie intake (2283.99 kcal vs. 3086.05 kcal, P<0.05) and serum levels of total cholesterol (95.19±0.61 mg/dl vs. 110.04±1.31 mg/dl, P<0.01), triglycerides (96.12±1.25 mg/dl vs. 105.99±1.29 mg/dl, P<0.01) while high-density lipoproteins levels were improved (42.15±0.92 mg/dl vs. 30.92±0.77 mg/dl, P<0.01) indicated its hypophagic and anti-hyperlipidemic effects. Conclusion: The gastroretentive floating pellets of anagliptin was obtained and could be a promising technique to deliver anagliptin with improved bioavailability in the management of the metabolic syndrome.

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Fructose-Drinking Water Induced Nonalcoholic Fatty Liver Disease and Ultrastructural Alteration of Hepatocyte Mitochondria in Male Wistar Rat

BioMed Research International ◽

10.1155/2015/895961 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 16

Author(s):

Norshalizah Mamikutty ◽

Zar Chi Thent ◽

Farihah Haji Suhaimi

Keyword(s):

Metabolic Syndrome ◽

Drinking Water ◽

Liver Disease ◽

Fatty Liver Disease ◽

Wistar Rats ◽

Wistar Rat ◽

Ultrastructural Changes ◽

Nonalcoholic Fatty Liver ◽

The Metabolic Syndrome ◽

Male Wistar Rats

Background.Nonalcoholic fatty liver disease (NAFLD) is one of the complications of the metabolic syndrome. It encompasses a wide range of disease spectrum from simple steatosis to liver cirrhosis. Structural alteration of hepatic mitochondria might be involved in the pathogenesis of NAFLD.Aims.In the present study, we used a newly established model of fructose-induced metabolic syndrome in male Wistar rats in order to investigate the ultrastructural changes in hepatic mitochondria that occur with fructose consumption and their association with NAFLD pathogenesis.Methods.The concentration of fructose-drinking water (FDW) used in this study was 20%. Six male Wistar rats were supplemented with FDW 20% for eight weeks. Body composition and metabolic parameters were measured before and after 8 weeks of FDW 20%. Histomorphology of the liver was evaluated and ultrastructural changes of mitochondria were assessed with transmission electron micrograph.Results.After 8 weeks of fructose consumption, the animals developed several features of the metabolic syndrome. Moreover, fructose consumption led to the development of macrovesicular hepatic steatosis and mitochondrial ultrastructural changes, such as increase in mitochondrial size, disruption of the cristae, and reduction of matrix density.Conclusion.We conclude that in male Wistar rat 8-week consumption of FDW 20% leads to NAFLD likely via mitochondrial structural alteration.

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The Establishment of Metabolic Syndrome Model by Induction of Fructose Drinking Water in Male Wistar Rats

BioMed Research International ◽

10.1155/2014/263897 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 45

Author(s):

Norshalizah Mamikutty ◽

Zar Chi Thent ◽

Shaiful Ridzwan Sapri ◽

Natasya Nadia Sahruddin ◽

Mohd Rafizul Mohd Yusof ◽

...

Keyword(s):

Metabolic Syndrome ◽

Drinking Water ◽

Rat Model ◽

Wistar Rats ◽

Calorie Intake ◽

The Metabolic Syndrome ◽

Male Wistar Rats ◽

Metabolic Syndrome Model ◽

One Way Anova ◽

Food And Fluid Intake

Background. Metabolic syndrome can be caused by modification of diet by means of consumption of high carbohydrate and high fat diet such as fructose.Aims. To develop a metabolic syndrome rat model by induction of fructose drinking water (FDW) in male Wistar rats.Methods. Eighteen male Wistar rats were fed with FDW 20% and FDW 25% for a duration of eight weeks. The physiological changes with regard to food and fluid intake, as well as calorie intake, were measured. The metabolic changes such as obesity, dyslipidaemia, hypertension, and hyperglycaemia were determined. Data was presented in mean ± SEM subjected to one-way ANOVA.Results. Male Wistar rats fed with FDW 20% for eight weeks developed significant higher obesity parameters compared to those fed with FDW 25%. There was hypertrophy of adipocytes in F20 and F25. There were also systolic hypertension, hypertriglyceridemia, and hyperglycemia in both groups.Conclusion. We conclude that the metabolic syndrome rat model is best established with the induction of FDW 20% for eight weeks. This was evident in the form of higher obesity parameter which caused the development of the metabolic syndrome.

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In vitro Release Kinetics Study of Ambroxol Hydrochloride Pellets Developed by Extrusion Spheronization Technique Followed by Acrylic Polymer Coating

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v7i1.1222 ◽

1970 ◽

Vol 7 (1) ◽

pp. 75-81 ◽

Cited By ~ 1

Author(s):

Ishtiaq Ahmed ◽

Monzurul Amin Roni ◽

Golam Kibria ◽

Muhammad Rashedul Islam ◽

Reza-ul Jalil

Keyword(s):

Drug Release ◽

Release Kinetics ◽

In Vitro Dissolution ◽

Acrylic Polymer ◽

Eudragit Rs ◽

Methacrylate Copolymer ◽

Ambroxol Hydrochloride ◽

Eudragit Rl ◽

Extrusion Spheronization

The aim of the present study was to investigate the effect of Ammonio Methacrylate Copolymer Dispersion Type A (Eudragit RL 30 D) and Ammonio Methacrylate Copolymer Dispersion Type B (Eudragit RS 30 D) combination in different weight ratios on the release kinetics of Ambroxol Hydrochloride from coated pellets. Microcrystalline cellulose, lactose, maize starch, hydroxypropyl methylcellulose and the drug was incorporated in the nuclei prepared by Extrusion-Spheronization technique which was coated with Eudragit RL 30D and Eudragit RS 30D in 1:1,1:1.5,1:2,1:2.5 and 1:3 ratios. The in vitro dissolution studies were carried out in 0.1N HCl for 1 hour followed by phosphate buffer (pH 6.8) for 11 h with USP dissolution apparatus Type-II. Drug release decreased with increasing amount of Eudragit RS 30 D in all cases. The drug release followed first order and Higuchi release kinetics. The Korsmeyer plot revealed n=0.50-0.61 or non-Fickian transport mechanism for drug release. From one way ANOVA it was found that the ratio of binary polymer mixer had significant (p < 0.05) effect on drug release. Key words: Aqueous coating, Eudragit, release kinetics, pellet, extrusion-spheronization Â DOI = 10.3329/dujps.v7i1.1222 Dhaka Univ. J. Pharm. Sci. 7(1): 75-81, 2008 (June)

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Oxidative Imbalance and Kidney Damage in Cafeteria Diet-Induced Rat Model of Metabolic Syndrome: Effect of Bergamot Polyphenolic Fraction

Antioxidants ◽

10.3390/antiox8030066 ◽

2019 ◽

Vol 8 (3) ◽

pp. 66 ◽

Cited By ~ 8

Author(s):

Daniele La Russa ◽

Francesca Giordano ◽

Alessandro Marrone ◽

Maddalena Parafati ◽

Elzbieta Janda ◽

...

Keyword(s):

Metabolic Syndrome ◽

Antioxidant Enzymes ◽

Kidney Disease ◽

High Plasma ◽

Cafeteria Diet ◽

The Metabolic Syndrome ◽

Oxidative Balance ◽

Apoptotic Pathways ◽

Stage Renal Disease ◽

End Stage

Obesity is a potent risk factor for kidney disease as it increases the possibility of developing diabetes and hypertension, and it has a direct impact on the development of chronic kidney disease and end-stage renal disease. In this study, we tested the effect of bergamot polyphenolic fraction in a cafeteria with diet-fed rats, an excellent experimental model for studying human metabolic syndrome, as it is able to induce severe obesity with insulin resistance and high plasma triglyceride levels more efficiently than a traditional lard-based high-fat diet used in rodent models. We analyzed the plasmatic oxidative balance by photometric tests, and the expression of cytoplasmic antioxidant enzymes (superoxide dismutase 1 and glutatione S-tranferasi P1) and apoptotic markers (Caspase 8 and 9) in kidney tissues by Western blot analysis. Our results clearly showed that the cafeteria diet induces a marked pro-oxidant effect: significant reduction of plasmatic antioxidant capacity; downregulation of cytoplasmic antioxidant enzymes expression; and activation of apoptotic pathways. All these hallmarks of redox disequilibrium were mitigated by treatment with polyphenolic fraction of bergamot, highlighting its antioxidant effect in the metabolic syndrome. Our data show that the link between obesity and renal damage could be represented by oxidative stress.

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Metabolic health in patients with schizophrenia – CVD risk in a Norwegian outpatient population

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1570 ◽

2017 ◽

Vol 41 (S1) ◽

pp. s810-s810

Author(s):

J. Engh ◽

E. Andersen ◽

E. Martinsen ◽

J. Egeland ◽

T.L. Holmen ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Metabolic Syndrome ◽

General Population ◽

Normal Population ◽

High Density Lipoproteins ◽

Cvd Risk ◽

Cross Sectional ◽

Metabolic Characteristics ◽

The Metabolic Syndrome

The mortality of schizophrenia patients is approximately twice that of the general population and there is a 20% reduction in life expectancy in this patient group. Cardiovascular disease (CVD) is responsible for as much as 50% of the excess mortality associated with schizophrenia. One important source of the high CVD prevalence is the cluster of metabolic characteristics defining the metabolic syndrome (MetS: 3 or more of the following features: abdominal obesity, high blood pressure, elevated levels of triglycerides and fasting glucose and low levels of high-density lipoproteins). Patients with schizophrenia seem to be undertreated for these vascular risk factors relative to the general population. More knowledge is needed concerning broadened risk factors of cardiovascular disease in a representative sample of schizophrenia patients. We conducted preliminary cross sectional analyses in a sample of 64 consecutive outpatients with schizophrenia with a mean age of 37 years consisting of 59% men, who were enrolled in a treatment study. All used antipsychotics, and 71% were smokers. We found that (percentage of patients under treatment for the respective somatic condition in parenthesis) 82% were overweight, 49% had hypertonia (17%), 24% hyperglycemia (3%), 48% hypertriglyceridemia and 13% hyperlipidemia (10% triglycerid or cholesterol lowering medication). Forty percent had metabolic syndrome compared to 11% in the normal population (Norway, age corrected). Additionally, estimates of insulin resistance will be conducted. We found that the prevalence of MetS components was high in outpatient schizophrenia. A substantial discrepancy was found between metabolic ill health and medication treatment of such conditions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Prevalence of Metabolic Syndrome and Its Components in Adults with Central Obesity at Janakpur Zone, Nepal

Journal of Nepal Health Research Council ◽

10.33314/jnhrc.v18i4.2890 ◽

2021 ◽

Vol 18 (4) ◽

pp. 681-685

Author(s):

Birendra Kumar Jha ◽

Mingma Lhamu Sherpa ◽

Binod Kumar Dahal ◽

Jitendra Kumar Singh

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Central Obesity ◽

International Diabetes Federation ◽

Cross Sectional Study ◽

High Density Lipoproteins ◽

Cluster Sampling ◽

Cross Sectional ◽

The Metabolic Syndrome

Background: Urbanization, surplus energy uptake, decreased physical activities are general risk factors of metabolic syndrome However, it’s status, and associated components remain unexplored in the Terai region of Nepal. This study evaluated the prevalence of metabolic syndrome and its components among adults with central obesity of Terai region of Nepal using International Diabetes Federation criteria.Methods: Community based cross-sectional study was conducted in three Terai districts of Janakpur Zone, Nepal. A total of 378 adults having central obesity were selected using cluster sampling by camp approach. Interview, physical and clinical examination, measurement of fasting blood sugar, and lipid profile were conducted for all participants. The prevalence of metabolic syndrome and its components with 95% CI were estimated.Results: The metabolic syndrome prevalence was 74.9% (95% CI:70.2-79.2%), with no significant differences between male (77.7%, 95% CI:71.0-83.5%) and female (72.2%, 95% CI: 65.2-78.3%). The most common factors observed were low high density lipoproteins with highly significant differences between male (77.7%, 95% CI:71.0-83.5%)) and female (90.2%, 95% CI: 85.094.0%-; p=0.001) and hypertriglyceridemia with significant differences between male (57.6%, 95% CI: 50.1-64.5%) and female (46.9%, 95% CI: 39.7-54.2%; p=0.037). Conclusions: Higher prevalence of metabolic syndrome and its risk factors in Janakpur of Nepal likely suggest lack of awareness and health promotion activities for metabolic syndrome and indicate an urgency for a public health program to maintain quality of life. Keywords: Metabolic syndrome; Nepal; prevalence; risk factors; terai

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Second Generation Antipsychotics (SGAs) in Schizophrenic Patients and Bipolar Disorder: Correlation With Metabolic Syndrome (NCEP ATP III(a))

Global Journal of Health Science ◽

10.5539/gjhs.v11n1p28 ◽

2018 ◽

Vol 11 (1) ◽

pp. 28

Author(s):

Consuelo Roldan Menco ◽

Anderson Díaz-Pérez ◽

Zoraida Barrios Puerta

Keyword(s):

Metabolic Syndrome ◽

Bipolar Disorder ◽

Second Generation ◽

Mental Illnesses ◽

Abdominal Circumference ◽

High Density Lipoproteins ◽

P Value ◽

Antipsychotic Treatment ◽

The Metabolic Syndrome ◽

Second Generation Antipsychotics

INTRODUCTION: The Metabolic Syndrome is a set of diverse clinical situations such as diabetes mellitus, hypertension and dyslipidemia. Patients with mental illnesses such as schizophrenia or bipolar disorder have a higher mortality than the general population attributable in 60% to somatic diseases and metabolic syndrome, where second generation antipsychotics increase the risk of weight gain and insulin resistance. Objectives. Correlate the treatment with second generation antipsychotics (SGAs) as a possible predictor for Metabolic Syndrome according to the NCEP ATP III (a) classification. METHODS: Descriptive, cross-sectional correlational study. The sample was of 92 patients, applying an open and convenience sampling due to the mental state of the patients in order to determine their degree of acceptance to the study (Informed Assent) and consent to the legal guardian as the main inclusion criterion. For the analysis, the following variables were considered: blood pressure, weight, height, abdominal circumference, serum levels of triglycerides, glucose and high density lipoproteins. The SPSS 20.0 ® program was used logistic regression analysis with a p-value <0.05 and a confidence level of 95%. RESULTS: SGAs most used was clozapine (54.3%). The correlation analysis showed that sociodemographic aspects such as personal history, habits, physical activity and paraclinical and anthropometric records correlated with the possible diagnosis of metabolic syndrome (p <0.05), but not with SGAs (p> 0.05). ). CONCLUSION: No correlation was found between the presence of the metabolic syndrome and the type of antipsychotic treatment.

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PATHOPHYSIOLOGICAL CHANGES IN LIVER TISSUES OF HYPERCALORIE DIET-INDUCED OBESE RATS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i1.15422 ◽

2016 ◽

Vol 10 (1) ◽

pp. 338 ◽

Cited By ~ 1

Author(s):

Bharatha Ambadasu ◽

Ramadevi S ◽

Naikawadi Aa ◽

Naveen Kumar M

Keyword(s):

Metabolic Syndrome ◽

Body Weight ◽

Wistar Rats ◽

Histopathological Examination ◽

Cafeteria Diet ◽

Nonalcoholic Fatty Liver ◽

Obese Rats ◽

Diet Intake ◽

Liver Tissues

ABSTRACTObjectives: Hypercalorie diet intake has been associated with many long-term complications including metabolic syndrome, cardiovascular diseases,and nonalcoholic fatty liver disease.Methods: A total of 12 Wistar rats either sex were used in this study. These animals were randomly divided into two groups as control and obese rats.Group 1 consists of six rats weighing 150-200 g and fed with normal pellet chow. Another six rats were fed hypercalorie/cafeteria diet to induce obesity andincluded in the study after 19 weeks of age. All animals were sacrificed; liver tissues were collected, weighed and sent for the histopathological examination.Results: Weight of liver tissues of was significantly more in obese rats than the control rats. Histopathological examination shows an excessive fatdeposition and sinusoidal congestion in the liver tissues of obese rats.Conclusion: Increase in body weight is associated with the increase in fat deposition in the liver tissues which further develops into inflammationand necrosis of liver cells.Keywords: Wistar rats, Hypercalorie/cafeteria diet, Obese rats, Histopathological examination.

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