Enhanced Bioavailability and Dissolution of Atorvastatin Calcium from Floating Microcapsules using Minimum Additives

Atorvastatin calcium, a lipid-lowering drug, is much less bioavailable because of reduced solubility in acidic media. Multiple-unit floating microcapsules of Atorvastatin calcium (ATC) were developed to expand the gastric residence time of the drug, as ATC has maximum rate of absorption in the upper GI tract. Floating microcapsules were prepared by Emulsion-solvent evaporation technique through incorporation of dioctyl sodium sulphosuccinate (DSS) as a dissolution enhancer. The microcapsules were assessed for shape, size, drug entrapment efficiency, stability and in-vitro drug dissolution rate and were subjected to SEM, DSC and PXRD studies. The ATC-loaded floating microcapsules were spherical in shape and had the particle size of about 28.10 μm and drug-loading efficiency of about 96.55 %. The floating microspheres containing DSS had significantly higher drug dissolution rates than those without DSS. The best formulation, AT4, consisting of Ethyl cellulose, DSS and Poly Ox®, had a maximum drug dissolution rate of 97.86 %, as compared to Storvas 80 mg (Ranbaxy Ltd, as a reference) which had a rate of only 54% during a period of 12 h in acidic media. A pharmacokinetic study performed on albino rabbits illustrates that the bioavailability of AT4 floating microcapsules significantly increased to nearly 1.7 times that of Storvas 80 mg. The present study indicates that the use of multi-unit floating microcapsules for delivery of ATC can improve its bioavailability

Hepatoprotective effects of methanol extract of Carissa opaca leaves on CCl4-induced damage in rat

<p>Abstract</p> <p>Background</p> <p><it>Carissa opaca </it>(Apocynaceae) leaves possess antioxidant activity and hepatoprotective effects, and so may provide a possible therapeutic alternative in hepatic disorders. The effect produced by methanolic extract of <it>Carissa opaca </it>leaves (MCL) was investigated on CCl₄-induced liver damages in rat.</p> <p>Methods</p> <p>30 rats were divided into five groups of six animals of each, having free access to food and water <it>ad libitum</it>. Group I (control) was given olive oil and DMSO, while group II, III and IV were injected intraperitoneally with CCl₄(0.5 ml/kg) as a 20% (v/v) solution in olive oil twice a week for 8 weeks. Animals of group II received only CCl₄. Rats of group III were given MCL intragastrically at a dose of 200 mg/kg bw while that of group IV received silymarin at a dose of 50 mg/kg bw twice a week for 8 weeks. However, animals of group V received MCL only at a dose of 200 mg/kg bw twice a week for 8 weeks. The activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and γ-glutamyltransferase (γ-GT) were determined in serum. Catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), glutathione reductase (GSR) and quinone reductase (QR) activity was measured in liver homogenates. Lipid peroxidation (thiobarbituric acid reactive substances; TBARS), glutathione (GSH) and hydrogen peroxide (H₂O₂) concentration was also assessed in liver homogenates. Phytochemicals in MCL were determined through qualitative and high performance liquid chromatography (HPLC) analysis.</p> <p>Results</p> <p>Hepatotoxicity induced with CCl₄was evidenced by significant increase in lipid peroxidation (TBARS) and H₂O₂level, serum activities of AST, ALT, ALP, LDH and γ-GT. Level of GSH determined in liver was significantly reduced, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GSR, GST and QR. On cirrhotic animals treated with CCl₄, histological studies showed centrilobular necrosis and infiltration of lymphocytes. MCL (200 mg/kg bw) and silymarin (50 mg/kg bw) co-treatment prevented all the changes observed with CCl₄-treated rats. The phytochemical analysis of MCL indicated the presence of flavonoids, tannins, alkaloids, phlobatannins, terpenoids, coumarins, anthraquinones, and cardiac glycosides. Isoquercetin, hyperoside, vitexin, myricetin and kaempherol was determined in MCL.</p> <p>Conclusion</p> <p>These results indicate that MCL has a significant protective effect against CCl₄induced hepatotoxicity in rat, which may be due to its antioxidant and membrane stabilizing properties.</p

Synchronous location-aware media and augmented visualization for real world tourist (SMART): An application for Khalifatabad heritage site, Bagerhat, Bangladesh

© 2016 IEEE. The ancient city of Khalifatabad in Bangladesh (also known as Bagerhat) is famous for Hazrat Khan Jahan Ali and his monumental creations of various mosques and mausoleum. UNESCO proclaimed Khalifatabad as a world heritage site in 1985. Driven by both cultural and religious interests, millions of local and foreign tourists visit this site every year. At present, there exist several historically significant mosques, mausoleum, residence, ruins, large water reservoirs, archaeological excavations and artifacts. However, due to limited knowledge about the local context, less accessibility to historic information, and the poor guiding system the visitors are unfortunately being kept from a deeper understanding of the cultural values of the site. In such context, this research aims to develop an application for handheld devices that can feed seamless authentic information and visual aids to the tourists for them to enjoy an engaging and immersive tour at Khalifatabad. A literature survey on existing apps reveals that most of the tools are developed for certain objectives and rarely fit for direct implementation at Khalifatabad. Therefore, the challenge remains twofold. First to develop a conceptual framework, which would help the tourists to have a deeper understanding of the significance of Khalifatabad. Second, to develop an application through adopting the conceptual framework. In this, the paper proposes a four-step conceptual framework i.e. 'SMART' (Synchronous Location-Aware Media and Augmented Visualization for Real-world Tourists) solution, for presentation of the information and user engagement. Supported by location-based service (LBS) and various data structure to feed different interactive features this framework sets the 'user-experience' at the top. Being part of an ongoing research project, this paper presents possible scenarios explaining how the seamless and synchronous information may help the real-world visitors to reveal the past in a compelling and memorable way, and how it may provoke better understanding and appreciation of the context. This paper expects that the proposed SMART solution will uphold the significance of Khalifatabad to the real-world visitors, besides, as a prototype; will open the possibilities of further use to the other heritage sites of Bangladesh

Insights into open/closed conformations of the catalytically active human guanylate kinase as investigated by small-angle X-ray scatteringand DAAD

Bio-catalysis is the outcome of a subtle interplay between internal motions in enzymes and chemical kinetics. Small-angle X-ray scattering (SAXS) investigation of an enzyme’s internal motions during catalysis offers an integral view of the protein’s structural plasticity, dynamics, and function, which is useful for understanding allosteric effects and developing novel medicines. Guanylate kinase (GMPK) is an essential enzyme involved in the guanine nucleotide metabolism of unicellular and multicellular organisms. It is also required for the intracellular activation of numerous antiviral and anticancer purine nucleoside analog prodrugs. Catalytically active recombinant human GMPK (hGMPK) was purified for the first time and changes in the size and shape of open/closed hGMPK were tracked by SAXS. The binding of substrates (GMP+AMPPNP or Ap5G or GMP+ADP) resulted in the compaction of size and shape of hGMPK. The structural changes between open and completely closed hGMPK conformation were confirmed by observing differences in the hGMPK secondary structures with circular dichroism spectroscopy

Desalting plasma protein solutions by membrane capacitive deionization

Plasma protein therapies are used by millions of people across the globe to treat a litany of diseases and serious medical conditions. One challenge in the manufacture of plasma protein therapies is the removal of salt ions (e.g., sodium, phosphate, and chloride) from the protein solution. The conventional approach to remove salt ions is the use of diafiltration membranes (e.g., tangential flow filtration) and ion-exchange chromatography. However, the ion-exchange resins within the chromatographic column, as well as filtration membranes, are subject to fouling by the plasma protein. In this work, we investigate membrane capacitive deionization (MCDI) as an alternative separation platform for removing ions from plasma protein solutions with negligible protein loss. MCDI has been previously deployed for brackish water desalination, nutrient recovery, mineral recovery, and removing pollutants from water. However, this is the first time this technique has been applied for removing 28% of ions (sodium, chloride, and phosphate) from human serum albumin solutions with less than 3% protein loss from the process stream. Furthermore, the MCDI experiments utilized highly conductive poly(phenylene alkylene) based ion exchange membranes (IEMs). These IEMs combined with ionomer coated nylon meshes in the spacer channel ameliorate ohmic resistances in MCDI improving energy efficiency. Overall, we envision MCDI as an effective separation platform in biopharmaceutical manufacturing for deionizing plasma protein solutions and other pharmaceutical formulations without loss of active pharmaceutical ingredients

Assessment of Contributing Factors and Treatment Practices for Therapeutic Efficacy and Drug-Related Problems in Suicidal Psychotic Patients

Suicide, a deliberate act of self-harm with the intention to die, is an emerging health concern but, unfortunately, the most under-researched subject in Pakistan, especially in Khyber Pukhtunkhwa (KPK). In this study, we aimed to identify risk factors that can be associated with suicidal behavior (SB) and to evaluate the prevailing treatment practices for therapeutic efficacy and drug-related problems (DRPs) in psychotic patients among the local population of KPK. A prospective, multicenter study was conducted for suicidal cases admitted to the study centers by randomized sampling. Socio-demographics and data on suicidal behavior were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), socioeconomic condition by Kuppuswamy socioeconomic scale (KSES) and treatment adherence by Morisky Medication-Taking Adherence Scale (MMAS-4). Drug-related problems and the therapeutic efficacy of prevailing treatment practices were assessed at baseline and follow-up after 3 months of treatment provided. Regarding suicidality (N = 128), females reported more ideations (63.1%), while males witnessed more suicidal behavior (66.6%, p p p = 0.004); dissatisfied with their life and had a previous history (p p = 0.001) than pharmacotherapy (p = 0.006) or psychotherapy (p = 0.183), alone. DRPs were also detected, including drug-selection problems (17.88%), dose-related problems (20.64%), potential drug–drug interactions (24.31%), adverse drug reactions (11.46%) and other problems like inadequate education and counseling (21.55%). Furthermore, it was also found that psychotic patients with suicidal ideations (SI) were significantly (p = 0.01) more adherent to the treatment as compared to those with suicidal attempts. We concluded that suicide attempters differed significantly from patients with suicidal ideations in psychotic patients and presented with peculiar characteristics regarding socio-demographic factors. A combination of therapies and adherence to the treatment provided better outcomes, and targeted interventions are warranted to address drug-related problems

Desalting Plasma Protein Solutions by Membrane Capacitive Deionization

Plasma protein therapies are used by millions of people across the globe to treat a litany of diseases and serious medical conditions. One challenge in the manufacture of plasma protein therapies is the removal of salt ions (e.g., sodium, phosphate, and chloride) from the protein solution. The conventional approach to remove salt ions is the use of diafiltration membranes (e.g., tangential flow filtration) and ion-exchange chromatography. However, the ion-exchange resins within the chromatographic column as well as filtration membranes are subject to fouling by the plasma protein. In this work, we investigate the membrane capacitive deionization (MCDI) as an alternative separation platform for removing ions from plasma protein solutions with negligible protein loss. MCDI has been previously deployed for brackish water desalination, nutrient recovery, mineral recovery, and removal of pollutants from water. However, this is the first time this technique has been applied for removing 28% of ions (sodium, chloride, and phosphate) from human serum albumin solutions with less than 3% protein loss from the process stream. Furthermore, the MCDI experiments utilized highly conductive poly(phenylene alkylene)-based ion exchange membranes (IEMs). These IEMs combined with ionomer-coated nylon meshes in the spacer channel ameliorate Ohmic resistances in MCDI improving the energy efficiency. Overall, we envision MCDI as an effective separation platform in biopharmaceutical manufacturing for deionizing plasma protein solutions and other pharmaceutical formulations without a loss of active pharmaceutical ingredients

Loading capacity versus enzyme activity in anisotropic and spherical calcium carbonate microparticles

A new method of fabrication of calcium carbonate microparticles of ellipsoidal, rhomboidal, and spherical geometries is reported by adjusting the relative concentration ratios of the initial salt solutions and/or the ethylene glycol content in the reaction medium. Morphology, porosity, crystallinity, and loading capacity of synthesized CaCO3 templates were characterized in detail. Particles harboring dextran or the enzyme guanylate kinase were obtained through encapsulation of these macromolecules using the layer-by-layer assembly technique to deposit positively and negatively charged polymers on these differently shaped CaCO3 templates and were characterized by confocal laser scanning fluorescence microscopy, fluorometric techniques, and enzyme activity measurements. The enzymatic activity, an important application of such porous particles and containers, has been analyzed in comparison with the loading capacity and geometry. Our results reveal that the particles’ shape influences morphology of particles and that, as a result, affects the activity of the encapsulated enzymes, in addition to the earlier reported influence on cellular uptake. These particles are promising candidates for efficient drug delivery due to their relatively high loading capacity, biocompatibility, and easy fabrication and handling