Optimization and Characterization Ezogabine-Loaded Nanosuspension for Enhancement of Bioavailability by “Bottom-Up” Technology Using 32 Factorial Design

Ezogabine, an antiepileptic drug used for treating partial epilepsies.  It is poorly soluble in water.  The dose ranges from 50 mg to 400 mg and the oral bioavailability is 60%.  The aim of this research work was to formulate and characterize nanosuspensions of ezogabine with an intention to enhance the oral bioavailability using 32 factorial design.   Nanosuspensions were prepared by the “bottom-up” nanoprecipitation method using 32 factorial design and evaluation for particle size, saturation solubility, zeta potential, entrapment efficiency, and in-vitro drug release was done.  The FTIR was used to confirm compatibility and to rule out any possible interactions between drug and carriers.  The optimal nanosuspension was obtained with particle size of 510.4 nm, saturation solubility of 557 μg/ml, zeta potential of - 4.49 mV, entrapment efficiency of 96.82%, and in-vitro drug release of 100.14%.  Also, the optimal formulation was found to be stable in the accelerated conditions.  Data of nanosuspensions were fit in to different equations and kinetic models and found to exhibit first order release kinetics with class II transport mechanism of diffusion.  The scanning electron microscopy studies showed elongated nanoparticles with porous surface.  The “Bottom up” method can be successfully employed to produce ezogabine nanosuspensions achieving reduced particle size and enhancing dissolution rate by increasing the saturation solubility and remained stable at 25 °C. Keywords: Nanosuspension, saturation solubility, bottom up

Formulation and Evaluation of Floating Tablets of Sitagliptin with Extract of Triphala

The aim of the present work is to formulate, optimize and evaluate hydrodynamically balanced antidiabetic system incorporated with sitagliptin and phytochemical constituents of Triphala extract for the treatment of constipation associated with diabetes.  The Triphala churna of two different ratios, 1:1:1 (TC1) and 1:2:4 (TC2) were subjected to hot percolation using Soxhlet apparatus using methanol as solvent. The floating matrix tablets of Sitagliptin with methanolic Triphala extract was prepared by wet granulation technique using HPMC K4M as polymer, starch/honey as binder and sodium bicarbonate & citric acid as effervescent agents by 24 factorial design.  The compatibility studies showed that there is no chemical interaction between the drug, polymer and the excipients used in the tablets.  The independent variables are drug & Triphala extract ratio (X1), Triphala proportion (X2), binder used for granulation (X3), and amount of effervescent excipients used (X4).  The dependent variables are hardness (Y1), buoyancy lag time (Y2), total floating time (Y3), in-vitro drug release (Y4), and T50% (Y5).  The prepared floating tablets were subjected to all post compression parameters such as hardness, friability, swelling capacity, buoyancy, total floating time, drug content & in-vitro drug release and were found to be within normal limits.  Based on drug content, buoyancy lag time and in-vitro drug release the formulations F14 and F16 were selected for in-vivo study of the formulation.  Keywords:  Triphala, Sitagliptin, honey, floating tablet.&nbsp

ACUTE TOXICITY AND IN-VIVO LAXATIVE STUDIES OF THE TRIPHALA EXTRACT IN EXPERIMENTAL ANIMALS

Triphala has been extensively used in traditional medicine for laxative, antidiabetic, expectorant, astringent, anti-aging etc.  The acute toxicity of methanolic extracts of Triphala in 300 mg, 600 mg, and 1000 mg/kg has not yet been studied.  The current studies were done by employing Swiss Albino mice as experimental animal. The methanolic extracts of Triphala were considered safe up to a dose of 1000 mg/kg when evaluated for acute oral toxicity in accordance with the OECD (Organization for Economic Cooperation and Development) guidelines. The results of acute toxicity showed no signs of toxicity such as general behaviour changes, mortality, changes on gross appearance or histopathological changes of the internal organs of rats. The examinations of signs of acute toxicity showed no abnormalities in the test groups as compared to the controls. Haematological and blood chemical values in treated groups were normal in comparison with the control group.  Therefore, the extract of Triphala given orally to mice did not produce acute toxicities.  The laxative activity on Albino Wistar rats shows that the Triphala extract has significant positive effect on constipated animals. &nbsp

CARBON NANOTUBE: A FLEXIBLE APPROACH FOR NANOMEDICINE AND DRUG DELIVERY

Nanostructures of carbon were first observed in 1952, which gained worldwide interest due to their various physicochemical properties. Carbonnanotubes (CNTs) have found wide applications in the delivery of therapeutic agents such as peptides, proteins, siRNA, nucleic acids, genes, vaccinesand also in bone and neural tissue regeneration. Functionalized CNTs have found to be biocompatible. The eye-catching features of these structuresare their electronic, mechanical, optical and chemical characteristics, which open a way to future applications and make them good candidates fora wide variety of applications, including drug transporters, new therapeutics, delivery systems and diagnostics. Their unique surface area, stiffness,strength, and resilience have led to much excitement in the field of pharmacy. They can pass through membranes, carrying therapeutic drugs, vaccines,and nucleic acids deep into the cell to targets that are previously unreachable. The applications of carbon nanotubes are in tissue engineering,drug carrier release system, wound healing, in cancer treatment and as biosensor. The successful realization of CNT-based biosensors requiresproper control of their chemical and physical properties, as well as their functionalization and surface immobilization. Real applications are stillunder development. The modifications are done to improve efficiency of carbon nanotubes by formulating luminescent carbon nanotubes, ultrathincarbon nano-needles, magnetically guided nanotubes. Researchers have recently developed a new approach to boron neutron capture therapy in thetreatment of cancer using substituted carborane-appended water-Soluble single-wall carbon nanotubes. This article provides an overview of currentnanotube technology, with a special focus on synthesis and purification, properties, benefits, and applications.Keywords: Carbon nanotubes, Biosensors, Tissue engineering, Biocompatible

Taurine Regulates Mitochondrial Function During 7,12-Dimethyl Benz[a]anthracene Induced Experimental Mammary Carcinogenesis

Objectives: The present study was undertaken to determine the modulatory effect of taurine on the liver mitochondrial enzyme system with reference to mitochondrial lipid peroxidation (LPO), antioxidants, major tricarboxylic acid cycle enzymes, and electron transport chain enzymes during 7,12-dimethyl benz[a]anthracene (DMBA) induced breast cancer in Sprague-Dawley rats. Methods: Animals in which breast cancer had been induced by using DMBA (25 mg/kg body weight) showed an increase in mitochondrial LPO together with decreases in enzymic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST)), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, and vitamin E), in citric acid cycle enzymes (isocitrate dehydrogenase (ICDH), alpha ketoglutarate dehydrogenase (alpha KDH), succinate dehydrogenase (SDH) and malate dehydrogenase (MDH)), and in electron transport chain (ETC) complexes. Results: Taurine (100 mg/kg body weight) treatment decreased liver mitochondrial LPO and augmented the activities/levels of enzymic, and non-enzymic antioxidants, tricarboxylic acid cycle enzymes and ETC complexes. Conclusion: The results of our present study demonstrated the chemotherapeutic efficacy of taurine treatment for DMBA-induced breast carcinomas