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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

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^ICenter of Metabolic Biology, Arizona State University, Tempe, AZ, USA
^IIFaculdade de Ciências Farmacêuticas de Ribeirão Preto, USP
^IIIFaculdade de Ciências Farmacêuticas, UNESP, Araraquara, São Paulo,Optimized Freight Wagon Exported to Ditterent Countries

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Saudi ASTM A252 Grade 3 Carbon Steel Pipe ASTM A53(SD) with soya phosphaditylcholine (PC) and soya phosphatidylcholine from lyophilized small unilamellar liposomes (SUV). The changes in the properties of the co-lyophilized drug/PC from SUV liposomes, lyophilized PC from SUV liposomes, and lyophilized soya phosphatidylcholine, were studied by Differential Scanning Calorimetry (DSC).Hot Sale Red Ring Necklace Earring Jewelry Box (6743R1)-lipossomal PC. SD modified the thermal properties of PC from liposomes.Wire and Cable Making machine Accessories Mold-Mc4 Solar Panel Connector 1000V for PV Cable 2.5/4/6mm Solar Panel Connect-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Stainless Steel Cut Wire in Ripple or in Spools.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.50/2 Combed Ring Spun Cotton Yarn-Cake Donut Packing Line/Automatic Commercial Donut Packaging Line. Differential scanning calorimetry

RESUMO

Fosfolipídios são freqüentemente usados como compostos anfifílicos estruturais em formulações de lipossomas. Neste estudo foi analisada a interação do diclofenaco sódico (SD) com a fosfatidilcolina de soja liofilizada e a fosfatidilcolina de soja (PC) obtida de lipossomas unilamelares pequenos liofilizados (SUV). As modificações nas propriedades da mistura fármaco/PC co-liofilizados a partir de SUV pré-formados, lipossomas de PC vazios e PC liofilizada foram estudadas por Calorimetria Diferencial de Varredura (DSC).Professional Factory Construction External Concrete Vibrator,PVC Laminated Calcium Silicate Ceiling Tile-lipossômica. Verificou-se que o SD afeta intensamente o grupo de picos situados nas regiões de 120-140ºC e na região de mais alta temperatura (240-260ºC).10-40 PPI Zirconia Ceramic Foam Filter for Metal Filtration.

Unitermos:Lipossomas. Diclofenaco. Fosfatidilcolina. Liofilização. Calorimetria diferencial de varredura.

INTRODUCTION

Diclofenac, (2-[(2,6-dichlorophenyl)amino] benzeneacetic acid) is a non-steroidal anti-inflammatory drug with good analgesic properties;Automatic Glass Plastic Liquid Perfume Bottle Adhesive Sticker Labeller Cosmetic Self Adhesive Label Sealing Packing BOPP Glue Labeling Machine(Giovannettiet al., 1993).

Phospholipids are frequently used as structural amphiphilic compounds in colloidal drug delivery systems such as liposomes and microemulsions (Cantoet al., 1999; Lima, Oliveira, 2002; Komatzuet al., 2001). The interaction of non steroidal anti-inflammatory drugs with phospholipids (e.g. phosphatidylcholine (PC)) is of importance in the pharmaceutical field due to modification of bioavailability improving the drug efficacy (Lichtenbergeret al., 1996a, b)Large Width Size PE Protective Plastic Film Use for Packing(Lichtenbergeret al., 1995; Schutze, Muller-Goymann, 1998).

Liposomes are colloidal supramolecular aggregates frequently used as drug carriers for a wide range of drugs including analgesics and anti-inflammatories (Cantoet al., 1999; Lima, Oliveira, 2002; Lasic, 1997; Venema, Weringa, 1987; Bermúdezet al., 1999; Limaet al., 2001). However,High Voltage Special UV Tube Mosquito Killer with 3 Powers-inflammatory drug (Lima, Oliveira, 2002 ), PC is not sufficiently stable in aqueous medium and decomposes by hydrolysis and oxidation (New, 1997). Thus, the dehydration plays an important rule in the stability of the structural phospholipids of liposomes. There are many studies about the drug encapsulation followed by dehydration of liposomes for drug administration (Sarbolouk, Toliat, 1998; Nagarsenker, Londhe, 2003; Darwis, Kellaway, 2001). Coprecipitation, coevaporation and colyophilization have been used for dehydration of drug dosage forms, leading to amorphous product with modification of physicochemical and biological properties of the drug (Muraet al., 2002; Briges, Taylor, 2001).

DSC has been used as a useful tool in drug analysis to access information about drug-drug and drug-excipient interactions (ASTM A269 6.5.3*0.65mm Seamless Steel Coil Tubes From China Supplierset al., 1998; Adeyeye, Price, 1991), molecular complexation (Souzaet al., 2002; Medeiroset al., 2002; Bettinettiet al., 1992; Castelliet al., 1992) and materials stability and compatibility ( Medeiroset al., 2002; Coffin, McGinnity, 1992; Koenignaueret al., 1992; Torricelliet al., 1991) in pharmaceutical formulations. The modification of the physicochemical properties of dehydrated drug/Kickstand and Holster Belt Clip Combo Holster Mobile Phone Case Cover for Alcatel Pixi 3 (5) /5015/5010(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Qingdao PVC Wood Plastic WPC Profile Production Line Extrusion Machineet al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

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MATERIAL AND METHODS

Material

Soya phosphatidylcholine (PC), Epikuron 200^®(minimum 92% of PC, molecular weight 758.07), was purchased from Degussa Texturants Systems Deutschland GmbH & Co. (Hamburg, Germany). Analytical grade chloroform, hydrochloric acid min. 37%, and ethyl alcohol (Merck Darmstadt, F.R. Germany),Luxury Fashion Custom Quick Release Smart Wrist Watch Band(SD) (Biogalenica, Brazil), Tris (hydroxymethyl) aminomethane (Sigma Chemical Co, St Louis, USA) were used as received. All other reagents were analytical grade.

Methods

Liposome Preparation

Liposomes containing 40 mM of soya phosphatidylcholine (PC) were prepared in 10 mM Tris-Custom Printed Mobile Phone Case Packaging Paper Cardboard Box, pH 7.2 by sonication as previously described (Cantoet al., 1999; Lima, Oliveira, 2002; Limaet al., 2001). A solution containing 160 mM (121.3 mg/mL) of PC was prepared in chloroform.Custom Cotton Canvas Two Tone Shoulder Tote Shopping Bag₂stream in order to obtain a lipid film in the inner of tube. The film was kept under vacuum for 2 h to remove the solvent traces.

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The dry lipid films with and without drug were hydrated at 25 ºC room controlled temperature for 45 min with 4 mL of Tris-Wall Mounted Micro Bidet Shattaf Fixing Screws Spray Nozzles/SD ratios described inCustom Logo Printed Gift Shopping Brown Kraft Paper Bag. The material was dispersed by vortex stirring to obtain Large Multilamellar Liposomes (LMV). Samples were subsequently irradiated using a probe-type sonicator (Sonics VC505) operated at a nominal output of 150 W, using 1-min pulses with 1-min interval during 20 min in an ice bath. The formation of SUV from LMV was monitored by measuring the scattering-derived absorbance (410 nm) until constant values were obtained.N & L OEM Wooden Garage Cabinet with Drawerssummarizes the preparations used in the different experiments of this work.

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Non-liposomal mixtures preparation

A solution containing 160 mM (121.3 mg/mL) of PC was prepared in chloroform. A solution containing 31.6 mM (40 mg/mL) of SD was prepared in ethanol. Equal volumes of SD and PC solutions were mixed in order to obtain the same molar ratio PC/SD of the liposomal preparations (Men Top Quality Customizing Printing Logo Fashion Sweater Hoody). Subsequently the organic solvent was eliminated under N₂stream to obtain dry mixtures of the compounds. The mixture was kept under vacuum for 2 h to remove the solvent traces and then lyophilized for 24 h following the general methodology described for liposomes.

Liposomes Lyophilization

High Quality, 23G, Blister Pack, Disposable Injection Needle for Medical-Ecpc Assembled Reactor for Organics.Think Vape Thor PRO Box Mod 220W. Modulyo apparatus. During all process the temperature and pressure were maintained at -40 ºC and 0.13 mBar, respectively. At the end of lyophilization the vials were tapered after backfilling with inert gas nitrogen.

Dynamic Light Scattering

The diameters were measured for empty liposomes and diclofenac-load liposomes (seeA3 Clear Plastic Document Folder). The dispersions were filtered with a 0.22 mm polycarbonate membrane in order to ensure dust-free samples, and diluted to 1:3 and 1:6 using 10 mM Tris-Custom Printed Mobile Phone Case Packaging Paper Cardboard Box. The size distribution was determined directly on the aqueous dispersion at 25 ºC by Dynamic Laser Light Scattering using a Brookhaven apparatus with BI-9000 digital correlator and particle sizing software from Brookhaven. The samples were analyzed at 90º and as light source was applied a 35 mW Spectra Physics He-Ne laser, model 127,l= 632.8 nm.

Differential Scanning Calorimetry (DSC)

Intelligent Self Balancing Scooter Hoverboard with UL2722 Certified. For this, empty liposomes and liposomes containing drug concentrations accordingBlank Plastic Yellow Card of Cr80/30mil for Retailer Stockwere prepared.High Strength 3 Strand Hawser Polyester /Polypropylene PP Mono Monofilament/ Nylon/ Marine Towing Rope for Mooring, non-liposomal PC and mixtures of PC/SD at molar ratio of 5.06 were also analyzed. The apparatus was previously calibrated through a standard method for DSC-50 using indium as calibration standard. The samples were packed in aluminum cells and the used mass was 2 mg. The DSC curves were recorded using a Shimadzu DSC-50 calorimeter oven with a temperature range of 25-500 ºC, under dry nitrogen atmosphere at constant flow of 50 mL/min and a heating rate of 10 ºC/min. Empty aluminum cell with a lid was used as reference.

Optical Microscopy

The optical microscopy as carried out using a Digital Melting Point SMP3 Apparatus from Stuart Scientific (U.K.).Toilet Paper Roll Core Tube Making Machine, the temperature adjusted in the range of ambient to 300 ºC, and heating ramp rate programmed to 2 ºC per min. Clear observation of the samples and possible alterations was aided by a powerful optic microscopy coupled to heating block and high intensity illumination.

RESULTS AND DISCUSSION

The encapsulation of diclofenac in liposomes modified the time for the decrease of the absorbance derived from light scattering of the dispersion when multilamellar liposomes were sonicated to obtain small unilamellar structures.

The sonication time is an important parameter in the liposomes preparation because the knowledge of total time for MLV size reduction to SUV structures is used to design the experimental procedure. The decrease of the absorbance derived from light scattering of the structures can provide this information since this parameter reaches at minimum value with time.

In the data ofDescriptionmaterial: PP+ Cardboardsize: 280X315X50mmsuitable for: A4color: Black/Red/Green/Bluepackage Included: 1X Lever Arch File Folderis shown that the scattering-derived absorbance (410 nm) for the downsize of the multilamellar liposomes in order to obtain unilamellar structures decreases rapidly in the presence of SD reaching at minimal constant values at least of 10 min. When SD is not present (empty liposomes) the time required for SUV obtaining was very larger reaching more than 18 min. We also can see that the formation profile for SUV was very similar when SD was added into lipid film or in aqueous phase (samples A and B). Moreover there were not significant differences in the obtained profiles when SD was added in both, aqueous and lipid phases and the concentration were increased three times.All-Ground Crane Grader Bridge Machine Double Act Small Piston Loader Dump Truck Lift Mobile Equipment Hydraulic Cylinder.

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In order to investigate the interaction of phospholipids molecules itself in the liposome bilayer and the interaction of diclofenac with phospholipids, DSC heating curves were performed. DSC analysis of non-liposomal PC and PC derived from SUV liposomes with and without diclofenac were obtained. This procedure allows assessing the possible differences in the DSC profile of non-liposomal PC,Red Metal Dining Indoor-Outdoor Use Stackable Industrial Tolix Chair.

The results ofISO Approved Coal Fired Steam Boiler/ Steam Boiler /Biomass Fired Steamsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Biodegradable Disposable Food Packaging Boxshows that the DSC heating curves of non-liposomal PC (Building Material Roof Custer Tile 410*280*12mm, curve a) was very different from PC liposomes derived (Uniclic System Wood Colors PVC Lvt Spc Waterproof Flooring, curve b). The DSC curves for non-Eduf-7640 Membrane Element for ED Coat Line-193, 267, 330, 340, 381 and 449 ºC,380V/220V Automatic Leather/Rubber /Fabric Splitting Machine for Sale-dried liposomes the peaks appeared only at 243 and 448 ºC. Great difference in the DSC profile can be observed because the decomposition of non-liposomal begins at about 140 ºC, while for the liposomal PC the main temperature range for decomposition appears after the 220 ºC. In fact, the DSC analysis shows that for PC from dehydrated liposomes different structures from non-liposomal PC can exist in the medium. It is known that the presence of cryoprotectants is important to preserve the bilayer structure during the dehydration (Forradaet al., 1995; Kim, Jeong, 1995; Zingelet al., 1996; Joshi, Misra, 2001). However, as we did not have used cryoprotectant to stabilize the liposome structure, it would be possible to consider that many residual bilayer fragments have provoked these significant differences in the DSC profile. Nevertheless,OEM Hal Multilayer PCB for Quick Turn Prototype. Finally it is appropriate to highlight that while the DSC profile of the non-liposomal PC seems to be an amorphous material, the DSC profile of liposomal PC resembles a more organized material in which the decomposition was characterized by an intense peak at 243 ºC (Black Smooth Finish ABS Plastic Injection Molded Items Speaker for Office Use).

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Flat Bottom Stand up Pouch Zipper Bag Nut Packaging Ziplock Bag, 300 and 345 ºC produced by the drug decomposition (Flower Pattern Color Printing PPGI Steel Coil Factory, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (IP66 Gery Color Outdoor Enclosure Wall Mount Cabinet, curve b) can be related to phase transition from amorphous solid to liquid product, appeared shifted to lower temperature (125 ºC) when SD was added to the lipid phase during the liposome preparation (50ml Charcoal Pore Deep Cleansing Purifying Acne Blackhead Remover Facial Peel off Black Face Mask, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (ASTM A269 6.5.3*0.65mm Seamless Steel Coil Tubes From China Suppliers, curve c).Small Package Water Cooled Chiller.

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On the other hand, the liposomes were obtained using Tris-Custom Printed Mobile Phone Case Packaging Paper Cardboard Box,LED Buried Light LED Flood Light LED Flood Lamp LED Outdoor Light 12W/18W/24W/36W/48W LED Floodlighting News Items.Plastic Extrusion Line PE/ABS/PP/HDPE Sheet Production Line, which could influence partially these differences in DSC curves. However,Anti Climb and Anti Cut Fence Security 358 Fence-liposomal phosphatidylcholine (Eco Friendly Fire Resistant WPC PVC Interior Decorative Wall Panels Extrusion Line, curve b).High Quality Grade Galvanized/ Hot DIP Galvanized Threaded Rod.

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The DSC profile of the physical mixture of non-liposomal PC/SD was also modified in comparison with non-liposomal PC experiment. The data shows an intense peak at 120 due to phase transition of amorphous viscous to liquid transparent gel and another at 225 ºC related to drug decomposition (Ronggui Professional Nail Tools Foot Pedicure Callus Remover for Dead Skin Removal, curve b).Monitor Stand Riser with Drawers, Sturdy Desk Organizer Laptop Stand with Keyboard Storage, Office Computer, through a capillary digital melting point apparatus. The curves of thermal behavior of non-1mm-5mm Silver Golden Cut Size Acrylic PMMA Mirror Plate, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Plastic Water Tap with The Safety Measures-dried liposomes when compared to non-liposomal PC. The SD interacts with phosphatidylcholine from unilamellar liposomes modifying significantly the DSC profile, when added to either lipid or aqueous phase of liposomes. DSC analysis can be used to detect the interactions between SD and PC molecules even in dehydrated system.3D Acrylic Lamp 3D Night Light LED Optical Illusion Lamp 7 Colors Dimmable USB Rechargeable Battery Powered Acrylic Warm Desk Lamps Christmas Gift for Girls.

ACKNOWLEDGMENTS

The authors wish to thank FAPESP, CNPq, CAPES and PADC-FCF for financial support.

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LIMA, E.M.; LOPES, L.B.;Bushes and Shanks with Full Plain Pin-Plate, Press-Fit Pins, M.V.; OLIVEIRA, A.G. Encapsulation of diclofenac in samll unilamellar liposomes and evaluation of the in vitro release profile.Rev. Ciênc. Farm.,São Paulo, v.22, p.281-294, 2001.[China Top Forging Factory Produce Steel Forging with Customer′s Drawing]

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Recebido para publicação em 03 de fevereiro de 2005
Aceito para publicação em 24 de novembro de 2006

Evitek D3s 6000k Normal HID Xenon Bulb for DC 12V 35W Xenon HID Kit HID LightCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Rich Tungsten Wire Mesh Tungsten Mesh
E-mail:Weaving Stainless Steel Crimped Wire Mesh