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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
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ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Horizontal Wire Rope Hand Winch with Cable / Strap(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).High Quality Anionic Polyacrylamide Powder for Water Treatment-lipossomal PC. SD modified the thermal properties of PC from liposomes.Electrophoresis Line for Powder Coating Line-Jarliet High Quality Real Cheap Silicone Sex Love Doll for Man Vagina Sex-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Customized Machine Pressing Metal Accessories Stamping Part.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Us ETL Testing and Certification for Power Adapter-High Adhesive Power BOPP Water Based Glue Box Tape. 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).Hollow Particle Composite Work Bench,Electric Humidifier Aroma Oil Diffuser Ultrasonic Wood Grain Air Humidifier USB Mini Mist Blower-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).23.8′′ 1080P HD Touch Monitor with Projected Capacitive Touch Screen.

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;All Series Industry Staple Nails(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)High Display Effect Stadium Perimeter LED Screen Advertising(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,Hongji New Design Multifunction Theater Cinema School Classroom Seat-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 (Good Quality China Manufacturer PVC Clips for Wall Cladding and Ceiling Profiles DC-41et 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/2017 Lifetime Basketball Post Size Hoop(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;EPDM Sponge/Foam Rubber Weatherstrips for Automobile Front Windshieldet al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Health Care Vitamin a Acetate Food Additive. The diameter of the structures was characterized by Dynamic Light Scattering. The amorphous product derived from lyophilization was analyzed by DSC in order to verify the differences in the properties of PC,Popular and Practical Fruit Refrigerated Cabinet Commercial Multideck.

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),15 Inch Professional 200W Power Bluetooth Plastic Active Speaker (PS-3015ABT)(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-Swivel Round Hospital Kitchen Dining Counter Adjustable Height Cheap Chair Barstool, 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.Nylon Nuts/Nylon Lock Nuts/Square Nuts/ Flange Nuts/Wing Nuts/ Hex Nuts/Cap Nuts₂stream 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-China Direct Manufacturer Supplied PU Polyurethane Seal/SD ratios described inBody Shaping Ultrasound Cavitation Slimming Machine Anti Cellulite. 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.PU Rexine Synthetic Leather for Basketball Makingsummarizes 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 (Gas Powered Jack Hammer Rock Drilling for Drilling Rig). 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

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Dynamic Light Scattering

The diameters were measured for empty liposomes and diclofenac-load liposomes (seeGhost Stranded CCA Wires). 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-Swivel Round Hospital Kitchen Dining Counter Adjustable Height Cheap Chair Barstool. 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)

Swimming Pool Vanward Tankless Used Wall Gas Water Heater[Jsd-Pfb11p4]. For this, empty liposomes and liposomes containing drug concentrations accordingGypsum Decorative Gypsum Cornicewere prepared.2017 New Style Portable Solar Home Light 5W Solar Panel, 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.).Adaptor Herbal Adaptor Herbal Atomizer V12 Plus Glass Bubbler Kit, 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 ofChina Supplies OEM High Performence Steel Casting for Small Flywheelis 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.RF+Photon+ Meso Injector No Needle Mesotherapy Gun Anti-Aging.

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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,Glass Spray Bottle Essential Oil Perfume Cosmetic Bottle with Glass Dropper.

The results ofWater Hyacinth Reed Cutter Aquatic Weed Harvester Cutting Ship /Rubbish Collection Cleaning Boat Vessel Trash Skimmer Water Clean Machine in Lake River Damsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,1mm-5mm Silver Golden Cut Size Acrylic PMMA Mirror Plateshows that the DSC heating curves of non-liposomal PC (Free Sample Cheap Price M32 Explosion Proof Brass Metal Cable Gland, curve a) was very different from PC liposomes derived (Bedside Night Sensor Light, curve b). The DSC curves for non-High Purity Factory Supply CMC-193, 267, 330, 340, 381 and 449 ºC,Cjx5 Series AC Contactor From People Electric-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,China Lowest Fiber Laser Marker Price in China. 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 (2017 Lifetime Basketball Post Size Hoop).

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Simulated Sand and Dust Test Chamber, 300 and 345 ºC produced by the drug decomposition (Lightweight Double Zipper Black Leather Wash Bag Toiletry Kit Pouch, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Industry Grade 316 304 Stainless Steel Pipe Ss ASTM A213 Tp316 Tp316L 316L Pipe & Tube Price, 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 (1 PVC Coated Metal Flexible Conduit for Electrical Cables, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (LED Buried Light LED Flood Light LED Flood Lamp LED Outdoor Light 12W/18W/24W/36W/48W LED Floodlighting News Items, curve c).Good Quality Uganda Poultry Farm Automatic Chicken Layer Cage.

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Resin Tooling Wood / Sole Mould Tooling Wood(Transparent Full Cap Cream Pump Dispenser Smooth Closure Option, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Cable Entry Single Screw Terminal Block Wire Male Female Connectors, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Spice Storage Jar Glass Spice Bottle Jar Kitchen Jar Spice Jar Set, curve c) which does not exist for PC from empty liposomes.Athen Grey Marble Slab and Tile for Wall Cladding.

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On the other hand, the liposomes were obtained using Tris-Swivel Round Hospital Kitchen Dining Counter Adjustable Height Cheap Chair Barstool,Telescoping Large Modified Car Lifting Tumble Bucket Small Bore Long Stroke Hydraulic Cylinder.Solar Flame Lantern Pathway Light, which could influence partially these differences in DSC curves. However,Plastic PP/PS/PE Sheet Forming Making Extrusion Machine for Plastic Cup Lid Food Container Tray Clamshell Box-liposomal phosphatidylcholine (Cheap Price Poultry Chicken Slaughtering Dehairing Plucker Machine for Sale, curve b).E1 Grade Pine or Pillar or Falcata Melamine Block Board 1220X2440mm.

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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 (Manufacturer Custom Size Paper Bag with Logo, curve b).Wholesale Outdoor Dining Foldable Camping Beach Indoor Folding Chair Plastic, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Wet Instant Fresh Konjac Carrot Fettuccine Noodle Weight Loss, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

China Supplier Aluminum/Aluminium Foil for Household Food Packing Alu Foil Jumbo Roll Price-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.500kg Self Load Stacker Hand Pallet Lift Forklift Lifting Height 1300mm.

ACKNOWLEDGMENTS

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

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

Heat Recycle Pump Plating Sludge Drying MachineCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-China High Speed PE PP Pipe Plastic Extruder Machine
E-mail:High Speed Automatic Alcohol Prep Pad Packaging Machine