FORMULATION AND IN VITRO EVALUATION OF DAPAGLIFLOZIN AND SAXAGLIPTIN BILAYERED TABLETS

Dapagliflozin (DG) is a sodium glucose cotransporter-2 (SGLT-2) inhibitor and Saxagliptin (SG) is a dipeptidyl peptidase-4 (DPP-4) inhibitor. The aim of the present work is to formulate a bilayered tablet (BT) of DG as immediate release (IR) layer and SG as sustained release (SR) layer by direct compression method for the effective treatment of type 2 diabetes mellitus. Type and concentration of superdisintegrant among [sodium starch glycolate (SSG)/Lycoat RS720/ Ludiflash] was optimized to enhance the dissolution rate (DR) of DG from the IR layer of BT. Type and concentration of SR polymer among (Carbapol 940/ Karaya gum/ HPMC K15M) was optimized to extend the release of SG up to 12 h with zero order release profile from the SR layer of BT. It was concluded that the optimization of the ratio of SG: SR polymer (HPMC K15M), had significant effect on extending the release profiles of SG. The ratio of SG: HPMC K15M at 1:18 respectively forms a better matrix for the extending the release of SG up to 12 h from the SR layer of BT. The optimized formulation; BT9 [IR9 (6% w/w Ludiflash as superdisintegrant and SR9 (with 60% HPMC K15M as SR polymer)] releases 100% of DG from the IR layer with in 45 min and extends the release of SG up to 12 h with a better zero order release profile (r2=0.994). It passes the accelerated stability studies as per ICH guidelines. A combination of these two classes [SGLT-2 inhibitors (DG) and DPP-4 inhibitors (SG)] of glucose-lowering agents and formulating them as a BT is more effective in the treatment and maintenance of type 2 diabetes mellitus

NOVEL CHRONOTHERAPEUTIC MULTIPARTICULATE DRUG DELIVERY SYSTEM OF FELODIPINE: AN EFFECTIVE TREATMENT FOR CARDIAC ARRHYTHMIA

Arrhythmia follows chronobiology, thus necessitating development of time-dependent formulation for its treatment. The aim of the current work was to develop a solubility-enhanced chronotherapeutic system of felodipine, a widely prescribed anti-arrhythmic. Systematically optimized hot-melt extrusion process was employed to formulate solubility-enhanced extrudates. Film-casting method was adopted for the selection of polymers. Drug released at 5, 15, 30min was taken as response variables in 32 face-centered cube design. Nearly 10-fold increase was observed in the solubility of the optimized extrudates in comparison to pure drug. Physical characterization of the extrudates depicted complete amorphization of drug. Sequential coating was performed on to the extrudates to enable a time-dependent release. In-vitro studies clearly demonstrated that 25% of drug was available rapidly within 10 min of administration. The remaining 75% of drug was available over a period of 4, 8 and 12h. Stability studies performed for 6 months at accelerated conditions depicted no significant change in the physicochemical characteristics of the optimized formulation. In-vivo pharmacokinetic studies conducted in beagle dogs ratified the results of in-vitro studies where a sequential time dependent absorption of felodipine was observed over a period of 12h. Concisely, the studies demonstrated successful development of solubility-enhanced chronotherapeutic system of felodipine

DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR THE ESTIMATION OF SITAFLOXACIN IN BULK AND PHARMACEUTICAL DOSAGE FORMS

Objective: A simple, specific, and precise reversed phase high performance liquid chromatography method was developed and validated as per the ICH guidelines for the determination of Sitafloxacin in bulk and tablet dosage forms.Methods: The quantitation was carried out by using Symmetry C18 ((5 µm, 100X4.6 mm) column at 300c with Water: Acetonitrile in ratio of 70:30 % V/V as mobile phase. The flow rate is 0.9 mL/min and the estimation was carried out by using PDA detector at 300 nm.Results: The retention time of Sitafloxacin was 2.198 minutes. The linearity was observed from 5-25 μg/mL with correlation coefficient 0.9999. The LOD and LOQ were found to be 0.429μg/mL and 1.415μg/mL respectively.Conclusion: The Statistics data for the Sitafloxacin was concluded that the method was found to be simple, reliable, selective, reproducible and accurate. The method was successfully used for quality control analysis of Sitafloxacin in bulk and Pharmaceutical dosage forms.Â

Pharmacognostic study of Argyreia pilosa stem

Background and objectives: Argyreia pilosa (Convolvulaceae) has been utilized for many aliments in the conventional system ethnomedicinally; most significantly against sexually transmitted diseases, skin troubles, diabetes, rheumatism, cough, and quinsy. The key challenge experienced in the standardization of herbal drugs is the correct identification of the plant source. Thus, setting up quality control parameters by means of pharmacognostic and phytochemical analysis which assures the purity, safety, and efficiency of A. pilosa is necessary. The current research was conducted to assess the pharmacognostic characteristics including macroscopic, microscopic, phytochemical and physicochemical parameters of the stems of A. pilosa. Methods: Micro as well as macroscopic characteristics were investigated. Physicochemical parameters had been done by implementing WHO suggested parameters; preliminary phytochemical and fluorescent evaluation of stem was executed for appropriate identification and standardization.  Results: The color, shape, size, odor and surface characteristics were reported from the stem and powdered stem material of A. pilosa. Light microscope images of cross section and powdered stem revealed the presence of phloem fibers, multicellular uniseriate trichomes, sclerides, lignified xylem fibers, xylem vessels, parenchyma cells and medullary rays. Phytochemical testing confirmed the presence of flavonoids, alkaloids, tannins, phenols, steroids, fixed oils, fats, acid compounds, glycosides, amino acids, and proteins. Physicochemical parameters such as moisture content, ash value, extractive value and fluorescent behavior of stem powder have also been established. Conclusion: The current research would be useful in order to supplement the information regarding to standardization, identity and in performing additional explorations in Ayurvedic system of medicine

EXPLORATION OF ANTI-HYPERGLYCEMIC AND HYPOLIPIDEMIC ACTIVITIES OF ETHANOLIC EXTRACT OF TINOSPORA CARDIFOLIA (WILD)HOOK WHOLE PLANT IN ALLOXAN INDUCED DIABETIC RATS

Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for diabetes mellitus. The aim of present study was to demonstrate the hypoglycemic and anti-diabetic activity of the Ethanolic extract of tinospora cardifolia whole plant in alloxan induced diabetic animals with a view to explore its use for the treatment of diabetes mellitus in humans. The Ethanolic extract of tinospora cardifolia whole plant was investigated for its anti-hyperglycemic and anti-hyperlipidemic effects in male albino rats. Diabetes was induced in the albino rats by administration of a single dose of alloxan monohydrate (150 mg/kg, bwt, i.p) and the Ethanolic extract of tinospora cardifolia whole plant was administered daily at single doses of 100 and 200 mg/kg, p. o to diabetes induced rats for a period of 14 days. The effect of Ethanolic extract of tinospora cardifolia whole plant on blood glucose level was measured in the diabetic rats. Serum lipid profiles [total cholesterol, triglycerides, phospholipids (low density, very low density and high density lipoprotein)] were also determined. The activities were also compared to the activity produced by a standard anti diabetic agent, Glibenclamide (500 μg/kg). The present investigation established pharmacological evidence to support the folklore claim that Ethanolic extract of tinospora cardifolia whole plant is an anti-diabetic agent. Keywords : Diabetes, Tinospora cardifolia,Alloxan, HDL,VLDL and fasting blood glucos

Optical Anisotropy in Bismuth Titanate: An Experimental and Theoretical Study

We report experimental and theoretical investigation of anisotropy in optical properties and their origin in the ferroelectric and paraelectric phases of bismuth titanate. Room temperature ellipsometric measurements performed on pulsed laser deposited bismuth titanate thin films of different orientations show anisotropy in the dielectric and optical constants, Subsequent first-principles calculations performed on the ground state structures of ferroelectric and high temperature paraelectric phases of bismuth titanate show that the material demonstrates anisotropic optical behavior in both ferroelectric and paraelectric phases. We further show that O 2p to Ti 3d transition is the primary origin of optical activity of the material while optical anisotropy results from the asymmetrically oriented Ti-O bonds in TiO6 octehdra in the unit cell.Comment: 13 pages, 4 figure

Meeting Report: Threats to Human Health and Environmental Sustainability in the Pacific Basin

The coastal zone of the Pacific Rim is home for about one-third of the world’s population. Disproportionate growth of Far Eastern economies has produced a disproportionate share of related environmental difficulties. As the region searches for acceptable compromises between growth and environmental quality, its influence on global environmental health is certain to increase. Consequences of global environmental change such as habitat alteration, storms, and sealevel rise will be particularly acute among Pacific Rim nations. Adverse health effects from arsenic exposure in Pacific Rim nations have been used to justify drinking water standards in the United States and elsewhere. As global manufacturing in the Pacific Rim increases, the centroid of global air quality and waste management issues will shift further toward Far Eastern nations. The Eleventh International Conference of the Pacific Basin Consortium (PBC) was held in September 2005 in Honolulu, Hawaii. The purpose of the conference was to bring together individuals to discuss regional challenges to sustainable growth. The historic emphasis of the conference on hazardous wastes in relation to human health makes the PBC an ideal forum for discussing technical aspects of sustainable economic growth in the Pacific region. That role is reflected in the 2005 PBC conference themes, which included management of arsenic in potable waters, air quality, climate change, pesticides, mercury, and electronics industry waste—each with emphasis on relationships to human health. Arsenic management exemplifies the manner in which the PBC can focus interdisciplinary discussion in a single technical area. The conference program provided talks on arsenic toxicology, treatment technologies, management of arsenic-bearing residuals from water treatment, and the probable societal costs and benefits of arsenic management

Data Resource Profile: Understanding the patterns and determinants of health in South Asians-the South Asia Biobank.

Funder: Singapore Ministry of Health's National Medical Research CouncilFunder: National Institute for Health ResearchFunder: Wellcome Trust or the Department of HealthFunder: NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme; Grant(s): IS-BRC-1215-2001

Rational Mutational Analysis of a Multidrug MFS Transporter CaMdr1p of Candida albicans by Employing a Membrane Environment Based Computational Approach

CaMdr1p is a multidrug MFS transporter of pathogenic Candida albicans. An over-expression of the gene encoding this protein is linked to clinically encountered azole resistance. In-depth knowledge of the structure and function of CaMdr1p is necessary for an effective design of modulators or inhibitors of this efflux transporter. Towards this goal, in this study, we have employed a membrane environment based computational approach to predict the functionally critical residues of CaMdr1p. For this, information theoretic scores which are variants of Relative Entropy (Modified Relative Entropy REM) were calculated from Multiple Sequence Alignment (MSA) by separately considering distinct physico-chemical properties of transmembrane (TM) and inter-TM regions. The residues of CaMdr1p with high REM which were predicted to be significantly important were subjected to site-directed mutational analysis. Interestingly, heterologous host Saccharomyces cerevisiae, over-expressing these mutant variants of CaMdr1p wherein these high REM residues were replaced by either alanine or leucine, demonstrated increased susceptibility to tested drugs. The hypersensitivity to drugs was supported by abrogated substrate efflux mediated by mutant variant proteins and was not attributed to their poor expression or surface localization. Additionally, by employing a distance plot from a 3D deduced model of CaMdr1p, we could also predict the role of these functionally critical residues in maintaining apparent inter-helical interactions to provide the desired fold for the proper functioning of CaMdr1p. Residues predicted to be critical for function across the family were also found to be vital from other previously published studies, implying its wider application to other membrane protein families