Formulation of Furosemide Oral Disintegrating Tablets Using Natural and Synthetic Superdisintegrants by SeDeM Expert Design System

SeDeM design expert technique used to evaluate the risks of poor flow of pharmaceutical powders under preformulation studies which reveals direct compression suitability and prepare robust composition of active pharmaceutical ingredient (API) and excipient in tablets formulation. The purpose of this study was to develop oral disintegrating tablets of Furosemide using different concentration of natural and synthetic superdisintegrants by means of SeDeM design technique. Oral disintegrating tablets (ODT) of Furosemide were prepared by direct compression technique using isolated banana powder and croscarmellose sodium (Ac-di-sol) together with microcrystalline cellulose as superdisintegrants. SeDeM design was performed to check suitability and deficient of excipients and drug for optimized composition derived based on IPP value. These tablets were evaluated for hardness, friability, drug content, weight variation, wetting time and in-vitro dissolution. All the formulations showed low weight variation with dispersion time less than 173.5±0.70 seconds and rapid in-vitro dissolution. The drug content of all the formulations was within the acceptable limits. Lubricated blend composition of F4 found average radius value 5.24, 0.66 and 5.509 for IGC, IP and IPP respectively, compressed tablet shown good physical properties. The optimized formulation F4 showed good release profile with 99.25 percentage drug release compared to other trial batches. It was concluded that natural superdisintegrant (banana powder) showed better disintegrating property than synthetic super disintegrant (Ac-di-sol) in the formulations of ODTs. Keywords: Furosemide, Oral disintegrating tablets, SeDeM expert system, Superdisintegrant

Impact of Six Sigma in a developing economy: analysis on benefits drawn by Indian industries

Overall operational excellence is the key requirement of any business to have global competence and sustained growth. Indian industries are not the exception to this. Six Sigma has emerged as one of the most effective business improvement strategies world wide. Nothing much has been published so far illustrating an overall experience of Indian industries with Six Sigma. This paper presents an analysis of the impact of Six Sigma on developing economy like India. The paper provides an insight into what kind of benefits Indian industries are gaining from Six Sigma as a whole. The study further highlights similarity and differences of benefit gained by different scales and sectors of Indian industries through Six Sigma. This exhaustive analysis of the benefits drawn by Indian industries through Six Sigma can assist other industries in India as well as those in other developing countries, who have yet not experimented with Six Sigma, to become more focused regarding their expectations from this improvement drivePeer Reviewe

Novel RP-HPLC method development and validation for simultaneous estimation of metformin, voglibose and pioglitazone in bulk and triple fixed drug combinations pharmaceutical dosage form

Reducing treatment complexity can be achieved through the use of single-tablet triple fixed-dose combinations of oral hypoglycemic agents. A simple, precise and accurate reverse-phase high-performance liquid chromatographic (RP-HPLC) method was developed and validated for the simultaneous determination of Metformin (MET), Voglibose (VOG) and Pioglitazone (PIO) in pharmaceutical dosage forms. Chromatographic separation was achieved on an Younglin (SK) gradient System with UV 730 D detector and Cosmosil C18 (250 x 4.6 mm, 5μm) column, maintained at 45°C using 0.1% v/v acetonitrile: triethylamine (30:70, v/v), pH 2.5 with flow rate 0.8 ml/min with injection volume at 20 μl and wavelength ultraviolet detection at 232 nm. MET, PIO and VOG obey Beer–Lambert’s law over the concentration range of 200-600 µg/ml, 30-90 µg/ml and 0.08-0.24 µg/ml, respectively, with regression equations y=2.021x -186.7 (MET) (R2 = 0.998), y=9.876x-202.31 (PIO) (R2 = 0.999),   and y= 502.3x-17.23 (VOG) (R2 = 0.999). % RSD and recoveries were 100.57-101.60 for MET, 99.79-102.61 for PIO and 100.02-101.05 for VOG indicate good accuracy of method. The marketed formulation analyzed using developed method and mean % amount were found 101.62, 100.38 and 98.75 for MET, PIO and VOG respectively with % RSD values NMT 2.0%. The developed spectrophotometric method can be employed for routine analysis of MET, VOG and PIO in bulk and tablet formulation. The developed RP-HPLC method was sensitive and selective for estimation of metformin, voglibose and pioglitazone in combined dosage form. The method was validated as per ICH guidelines. Keywords: RP-HPLC, ICH guidelines, Metformin, Voglibose, Pioglitazone, Validatio

FABRICATION AND OPTIMIZATION OF NOVEL GLIPIZIDE SUSTAINED RELEASE MATRICES FOR SOLUBILITY AND DISSOLUTION ENHANCEMENT BY SOLID DISPERSION THROUGH HYDROPHILLIC CARRIERS

The present research work was to improve the dissolution rate of glipizide which belongs to BCS II drug by enhancing its aqueous solubility using different hydrophilic carriers like PEG 6000 and hydroxypropyl methylcellulose E15 (HPMC E15). The solid dispersion was embedded into the matrix of polymers to sustain the release pattern of drug. The various solid dispersion formulations were prepared by employing fusion method using different carriers. Further solid dispersion formulations were subjected to different in-vitro evaluation tests for solubility, drug content uniformity, drug-polymer interaction, DSC study and in-vitro drug release study. Tablets were prepared by direct compression method and evaluated for various physical parameters. A direct compression method using response surface methodology, followed by optimization of the evaluated parameters was employed to get the final optimized formulation. The results of drug content uniformity showed the uniform dispersion of glipizide in solid dispersion formulations. The DSC endothermic peak at 216.08°C due to glipizide was partially and completely disappeared in solid dispersion formulation indicating that drug was completely dispersed in formulations. In-vitro drug release showed 80.35% in 60 minutes for the best solid dispersion formulation S3 (ratio 1:3). Among all the formulations, F4 shows 92.87% better sustained release at the end of 12 hrs. The release co-efficient values ‘n’ (Ë‚0.5) indicated that the drug release followed fickian diffusion mechanism based on formulation factors. The stability studies were carried out according to ICH guideline and result found of selected formulation was stable.Keywords: Glipizide, Solid dispersion, Xanthan gum, MatricesÂ

Mitochondrial alpha-ketoglutarate dehydrogenase complex generates reactive oxygen species

Mitochondria-produced reactive oxygen species (ROS) are thought to contribute to cell death caused by a multitude of pathological conditions. The molecular sites of mitochondrial ROS production are not well established but are generally thought to be located in complex I and complex III of the electron transport chain. We measured H 2 O 2 production, respiration, and NADPH reduction level in rat brain mitochondria oxidizing a variety of respiratory substrates. Under conditions of maximum respiration induced with either ADP or carbonyl cyanide p -trifluoromethoxyphenylhydrazone, � -ketoglutarate supported the highest rate of H 2 O 2 production. In the absence of ADP or in the presence of rotenone, H 2 O 2 production rates correlated with the reduction level of mitochondrial NADPH with various substrates, with the exception of � -ketoglutarate. Isolated mitochondrial � -ketoglutarate dehydrogenase (KGDHC) and pyruvate dehy- drogenase (PDHC) complexes produced superoxide and H 2 O 2 . NAD � inhibited ROS production by the isolated enzymes and by perme- abilized mitochondria. We also measured H 2 O 2 production by brain mitochondria isolated from heterozygous knock-out mice deficient in dihydrolipoyl dehydrogenase (Dld). Although this enzyme is a part of both KGDHC and PDHC, there was greater impairment of KGDHC activity in Dld-deficient mitochondria. These mitochondria also produced significantly less H 2 O 2 than mitochondria isolated from their littermate wild-type mice. The data strongly indicate that KGDHC is a primary site of ROS production in normally functioning mitochondria

Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component of human ketoacid dehydrogenase complexes

cDNA clones comprising the entire coding region for human dihydrolipoamide dehydrogenase (dihydrolipoamide:NAD+ oxidoreductase, EC 1.8.1.4) have been isolated from a human liver cDNA library. The cDNA sequence of the largest clone consisted of 2082 base pairs and contained a 1527-base open reading frame that encodes a precursor dihydrolipoamide dehydrogenase of 509 amino acid residues. The first 35-amino acid residues of the open reading frame probably correspond to a typical mitochondrial import leader sequence. The predicted amino acid sequence of the mature protein, starting at the residue number 36 of the open reading frame, is almost identical (greater than 98% homology) with the known partial amino acid sequence of the pig heart dihydrolipoamide dehydrogenase. The cDNA clone also contains a 3' untranslated region of 505 bases with an unusual polyadenylylation signal (TATAAA) and a short poly(A) track. By blot-hybridization analysis with the cDNA as probe, two mRNAs, 2.2 and 2.4 kilobases in size, have been detected in human tissues and fibroblasts, whereas only one mRNA (2.4 kilobases) was detected in rat tissues

How Unpopular Policies are Made: Examples from South Africa, Singapore, and Bangladesh

In this article we contribute to the emerging knowledge on migration policy?making in two ways. Firstly, we address the relative lack of research on the gendered nature of migration policy?making. Secondly we contribute to understanding migration policymaking in postcolonial contexts. Based on case studies from Bangladesh, South Africa, and Singapore, we trace the drivers of policy change in these contexts and how the gendered vulnerability of the intended beneficiaries impacted the policy process. We found that there were four main drivers of migration policy?making in each of the countries. They were: the role?players in the policy change process, the debates that shaped the policy change, the research involved, and the political context in which the policy change took place. While our research drew on existing policy frameworks, it also showed that policy development is shaped by complex socio?political conditions.DFIDMigrating out of Povert

Impact of Six Sigma in a developing economy: analysis on benefits drawn by Indian industries

Overall operational excellence is the key requirement of any business to have global competence and sustained growth. Indian industries are not the exception to this. Six Sigma has emerged as one of the most effective business improvement strategies world wide. Nothing much has been published so far illustrating an overall experience of Indian industries with Six Sigma. This paper presents an analysis of the impact of Six Sigma on developing economy like India. The paper provides an insight into what kind of benefits Indian industries are gaining from Six Sigma as a whole. The study further highlights similarity and differences of benefit gained by different scales and sectors of Indian industries through Six Sigma. This exhaustive analysis of the benefits drawn by Indian industries through Six Sigma can assist other industries in India as well as those in other developing countries, who have yet not experimented with Six Sigma, to become more focused regarding their expectations from this improvement drivePeer Reviewe

Cerebral Developmental Abnormalities in a Mouse with Systemic Pyruvate Dehydrogenase Deficiency.

UNLABELLEDPyruvate dehydrogenase (PDH) complex (PDC) deficiency is an inborn error of pyruvate metabolism causing a variety of neurologic manifestations. Systematic analyses of development of affected brain structures and the cellular processes responsible for their impairment have not been performed due to the lack of an animal model for PDC deficiency.METHODSIn the present study we investigated a murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene encoding the α subunit of PDH to study its role on brain development and behavioral studies.RESULTSMale embryos died prenatally but heterozygous females were born. PDC activity was reduced in the brain and other tissues in female progeny compared to age-matched control females. Immunohistochemical analysis of several brain regions showed that approximately 40% of cells were PDH(-). The oxidation of glucose to CO2 and incorporation of glucose-carbon into fatty acids were reduced in brain slices from 15 day-old PDC-deficient females. Histological analyses showed alterations in several structures in white and gray matters in 35 day-old PDC-deficient females. Reduction in total cell number and reduced dendritic arbors in Purkinje neurons were observed in PDC-deficient females. Furthermore, cell proliferation, migration and differentiation into neurons by newly generated cells were reduced in the affected females during pre- and postnatal periods. PDC-deficient mice had normal locomotor activity in a novel environment but displayed decreased startle responses to loud noises and there was evidence of abnormal pre-pulse inhibition of the startle reflex.CONCLUSIONSThe results show that a reduction in glucose metabolism resulting in deficit in energy production and fatty acid biosynthesis impairs cellular differentiation and brain development in PDC-deficient mice

Maternal Pea Protein Intake Provides Sex-Specific Protection against Dyslipidemia in Offspring from Obese Pregnancies

Increased consumption of dietary pulse protein has been shown to assist in body weight regulation and improve a range of metabolic health outcomes. We investigated if the exchange of casein for yellow pea protein (YPPN) in an obese-inducing maternal diet throughout pregnancy and lactation offered protection against obesity and dyslipidemia in offspring. Sixty female Sprague Dawley rats were fed a low-calorie control diet (CON), a high-caloric obesity-inducing diet (with casein protein (CP), HC-CP), or an isocaloric/macronutrient-matched HC diet supplemented with YPPN isolate (HC-PPN) in pre-pregnancy, gestation, and lactation. Body weight (BW) and metabolic outcomes were assessed in male and female offspring at weaning and in adulthood after consuming the CON diet in the postnatal period. Consumption of the HC-PPN diet did not protect against maternal obesity but did improve reproductive success compared with the HC-CP group (72.7% versus 43.7%) and reduced total energy, fat, and protein in maternal milk. Male, but not female, offspring from mothers fed the HC-CP diet demonstrated hyperphagia, obesity, dyslipidemia, and hepatic triglyceride (TG) accumulation as adults compared with CON offspring. Isocaloric exchange of CP for YPPN in a high-calorie obese-inducing diet did not protect against obesity but did improve several aspects of lipid metabolism in adult male offspring including serum total cholesterol, LDL/VLDL cholesterol, triglycerides (TGs), and hepatic TG concentration. Our results suggest that the exchange of CP for YPPN in a maternal obese-inducing diet selectively protects male offspring from the malprogramming of lipid metabolism in adulthood