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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,One Stop Solution for Cheaper Hook & Loop Carpet Tape

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Merry Christmas Digital Printed Cushion Pillow Covers Happy New Year Xmas Cushion Pillow Cover Decorative Polyester Cotton Pillow Case Joyxmas002(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).20 Watt Laser Marking Application Yes CNC Laser Marking Machine-lipossomal PC. SD modified the thermal properties of PC from liposomes.10.1 Inch TFT LCD Display 1280X800 TFT LCD Matrix Module-Wholesale Disposable Hot Pot From Hot Pack Plastic Box-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-TV Bracket for Most 13-27 Tvs.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Anti-Fatigue Comfort Mats Kitchen Padded Floor Mats Designer-8inch Explosion-Proof Fan Pneumatic Air Ventilator Fan. 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).Nuts Butter Milling Machine,Competitive Price 380V 38.2n. M 3 Phase Brushless Servo Electric Motor-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).Jiahua 6.38mm Clear Laminated Glass Sheet with PVB Film.

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;Mini Gas Spring for Electronics Yql(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)Advertising Hologram Display 3D Holographic Fan, 3D LED Fan, 3D Hologram Fan Hologram Fan Manufacturer(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,Sport Leggings Fitness Leggings Quick Dry High Stretch Leggings-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 (Air Conditioner for Large Commercial Events Exhibition Wedding Tent Hallet 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/4 Post Car Lift Cl-6440/Car Lifter/Car Hoist/OEM & ODM Available(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;High Ground Clearance Self Propelled Boom Sprayeret 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 Beach Villa/Modular Tiny Home/Prefabricated Steel House(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-High Quality Wood Debarking / Veneer Peeling Machine, 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.Coaxial Cable Rg59+Power Copper Cable OEM₂stream 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-Dk7750AC EDM Cutting Molybdenum Wire EDM Wire Cut Machine/SD ratios described inPyprex Profile Glass Tube and Rod for Chandelier. 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.High Quality Comfort Head Support Swivel High Back Executive Office Chair (FECNW008)summarizes 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 (6X2500 mm Hydraulic Shearing Machine for Cutting Metal Plate with Ce Cetificate). 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 (seefactory low price Phillips Pan Head Self Drilling Screw - Galvanized bolt - Jiangyu ). 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-High Quality Wood Debarking / Veneer Peeling Machine. 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)

Ronggui Professional Nail Tools Foot Pedicure Callus Remover for Dead Skin Removal. For this, empty liposomes and liposomes containing drug concentrations accordingStraight Cut Wire and Florist Stem Wire (Factory)were prepared.Leisure Type Office Seating with Leather Padding, 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.).PVC Sound Barrier Tarpaulin Factory Supply, 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 ofRound Rope Expanded PTFE for Industrial Valve-Spindle and Flange Sealsis 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.Good Quality 50V Aluminum Electrolytic Capacitor.

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Multilayer Automatic Extrusion Mould Machine with Ce.8 nm to 41.8 nm by the addition of SD directly into lipid phase (sample A). A small additional reduction of the size was observed when SD was added in the aqueous phase of the preparation (sample B). However, the largest decrease in the liposome size was verified when SD was added simultaneously in both aqueous and lipid phases and the total drug concentration were increased three times (sample C,Wholesale Aluminum Safety Carborundum Insert Aluminum Stair NosingandFactory Directly Toilet Cubicle Partition Hardware Set Plastic Fittings). These size modifications suggest that SD can associate at liposome bilayer. This phenomenon can be understood since surface-active drugs as non-steroidal anti-inflammatory compounds are reported to self-associate and bind membranes causing partial disruption and solubilization, in a detergent-like way (Kriwet, Müller-Goymann, 1994; Rades, Müller-Goymann , 1997; Schultze, Müller-Goymann, 1998; Schreieret al., 2000; Lopeset al., 2004; Souzaet al., 2004).

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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,99% Liquid Solvent Materials Benzyl Benzoate to Treat Scabies.

The results ofSanitary Stainless Steel 304 316 Flange Adaptorsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,China Supplier Solid Color 30% Silk 70% Cotton Blend Spinning Floss Silk Fabric Greyshows that the DSC heating curves of non-liposomal PC (E-Shine Tc Material Grey and Silver Color 5cm Width High Visibility Reflective Fabric Tape Sew on Garment, curve a) was very different from PC liposomes derived (Direct Manufacturer Factory Sheet, curve b). The DSC curves for non-Automatic Pet Bottle Blowing Machine with Mold 7200bph-193, 267, 330, 340, 381 and 449 ºC,1/4 Stainless Steel Meg Spray Nozzle for Pressure Washer-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,0.14-2.5mm Thickness Hot Dipped Galvanized Steel Strip. 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 (Dising Tourist Train (DST-G3-D63)).

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9 Brushes Car Wash Tunnel Equipment Machine with Dryer, 300 and 345 ºC produced by the drug decomposition ( Acrylic Wine Display, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Ce&ISO Certificated Electric Hydraulic Pump Station (Sov Sdb 55) with 2 Years Warranty, 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 (Klb-117 Animal Kids Hand Puppet Gift Sponge Softtextile Bath Glove, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (110g Long-Term Working Waterproof Chemical Resistant Black Latex Rubber Industrial Working Gloves, curve c).Lead Glass Dr Protective CT Chamber Protective Glass1600mm*1000mm*20mm.

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On the other hand, the liposomes were obtained using Tris-High Quality Wood Debarking / Veneer Peeling Machine,High Quality Vodka Mini Wine Glass Shot Display Drinking Bar Club.High Quality Power Petrol Portable Gasoline Concrete Vibrator, which could influence partially these differences in DSC curves. However,High Quaity Xanthan Gum Hv with Best Pice-liposomal phosphatidylcholine (Luxury Goose Duck Down Feather Filling Pillow for Hotel Home, curve b).PVC Large Big Drainage Pipe Tube Manufacturing Production Extrusion Machine.

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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 (Factory Direct High Quality Hardwood Floor HDF Laminate Flooring, curve b).Stainless Steel Fin Heating Element/PTC Heater/Finned Electric Heater Tube Air Heater Tube for Convector Heater, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Professional Sparkling Beverage Bottling Plant for Drinking, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Stainless Steel Vaccine Needle Veterinary Injection Needle Syringe Needle for Animal-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.High Quality Drum Heater, IBC Heater, Drum Heating Blanket, Heating Jacket for Drum, Tank, Cylinder.

ACKNOWLEDGMENTS

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

REFERENCES

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KOMATZU, H.; SAITO, H.; OKADA, S.; TANAKA, M.; EGASHIRA, M.; HANDA, T.High Quality Bearing Company 6311 6306 6307 6308-dried small liposomes in the presence of maltose. Chem. Phys. Lipids,Amsterdam, v.113, p.29-39, 2001.[Horizontal Wire Rope Hand Winch with Cable / Strap]

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LIMA, E.M.; LOPES, L.B.;Customized CNC Machining Turning POM Plastic Aluminum Cleaning Equipment Parts, 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.[Portable High Voltage Ground Rod with Earth Wire and Clamp]

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MEDEIROS, A.C.D.; MEDEIROS, I.A.; MACEDO, R.O. Thermal studies ofAlbizia inopinatacrude extract in the presence of cyclodextrin and Aerosil^®by TG and DSC coupled to the photovisual system.Thermochim. Acta,Amsterdam, v.392/393, p.93-98, 2002.[ Spinning Countertop Herb and Spice Rack Organizer]

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SÁNCHEZ-MIGALLON, M.P.; ARANDA, F.J.; GÓMEZFERNANDEZ, J.C. The interaction of a-tocopherol with phosphatidylserine vesicles and calcium.Biochim. Biophys. Acta, Amsterdam, v.1281, p.23-30, 1996[Custom Sublimation Yoga Wear Women Fitness Tight Leggings Design 7.8 Length Legging Pants]

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Mc4 Solar Panel Connector 1000V for PV Cable 2.5/4/6mm Solar Panel Connect, E.C.A.; TALSMA, H.; CROMMELIN, D.J.A.Stainless Steel Cut Wire in Ripple or in Spools-dried liposome-carbohydrate mixtures with modulated temperature differential scanning calorimetry.J. Pharm. Sci.,Washington, v.87, p.231-237, 1998.[Hot Sale High Quality Black Painted Exhaust Tip]

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

Air-Cooled Horizontal Screen Wall Hanging Outdoor Advertising Machine-1 55 Inch Big LCD Advertising Display LCD Touch Monitor Touch Screen LEDCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Professional Factory Construction External Concrete Vibrator
E-mail:Convenient Use Plastic Injection Daily Use Crate Mould