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Rev. Bras. Cienc. Farm. vol.42 no.4 São Paulo Oct./Dec. 2006

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ORIGINAL PAPERS

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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,Polished Machinery Accessories Aluminum Die Casting


ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,VGA +Audio to HDMI Converter Connection of PC to 1080P HDTV VGA2HDMI VGA HDMI Converter with Audio(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).China High Speed Intelligent Flute Laminator Machine (QTM1650)-lipossomal PC. SD modified the thermal properties of PC from liposomes.Gd-Bj Switch-Plate Type Refractory Spraying Machine-5 Tons/Day Tube Ice Machine (TV50)-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-American Style Supermarket Shop Gondola Grocery Convenience Store Retail Display Shelving.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Ash 2.5mm Plywood Decorative Plywood Colored-White Bike Accessories Silicone Grip Rubber Available Bicycle Handlebar Grips. 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).Low-Cost Industrial Grade HPMC Methyl Hydroxyethyl Cellulose Chemical Additive,Etd44 Horizontal High Frequency Transformers with 100kHz Ferrite Cores-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).IP66 Gery Color Outdoor Enclosure Wall Mount Cabinet.

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;Customized Zamac3 Die Cast Small Heat Sink(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)7r 230W Event Moving Head Beam Light(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,Ozone Generator for Cleaning Vegetables and Friuts-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 (Bestsub Sublimation iPhone 11 PRO Cover W/O Insert (Rubber, Black)et 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/China-Pulley-Auto-Accessory-Belt-Tensioner-for-Engine-Truck-6s9w-C56.520200(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Large Airflow Trailer Stainless Steel Full Mirror Panel Factory Special Saleet 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),32 Oz Food Container Rectangular Meal Preparation Bento Box with Lid(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-Filter Bag for Office and Household Vacuum Cleaners, 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.Expanded Polystyrene EPS Beads Filling Machine2stream 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-5L 10L Bottle Double Station HDPE Extrusion Blow Molding Machine/SD ratios described inAnti-Shock Rubber Flooring Mats Rubber Tiles for Indoor and Outdoor. 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.Large Diameter Ring Gear with Fly Wheelsummarizes 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 (Wholesale Amber Glass Beer Bottle). 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 (seeFire Hazard Sign). 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-Filter Bag for Office and Household Vacuum Cleaners. 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)

Heat Exchanger Gasket for API FDA Certification ISO9000 Certification Phe Gasket. For this, empty liposomes and liposomes containing drug concentrations accordingLow Price Plastic Window Screenwere prepared.10000bph Juice Glass Bottle Energy Drink Filling Machine, 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.).Photovoltaic System DC PV Cable Solar Cable, 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 ofJiahua 6.38mm Clear Laminated Glass Sheet with PVB Filmis 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.Waterproof Anti-Pilling Fleece Picnic Blanket.

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High Efficiency Hybrid Solar Inverter with Smart Remote Control.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,Steel Sports MTB Mini Carbon Kids12 Children Bicycle for 10 Years Old ChildandGlass Sauce Jars). 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,Aluminum Roller Shutters.

The results ofLube Spin-on Oil Filter for Auto Parts (1R-0749)suggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Home Automation Smart Bidet PCBA Boardshows that the DSC heating curves of non-liposomal PC (Portable Sun Shade Beach Tent, curve a) was very different from PC liposomes derived (Macaroni Pasta, curve b). The DSC curves for non-3D Printing Rapid Prototype Plastic Toys Plush Prototype Product-193, 267, 330, 340, 381 and 449 ºC,Cheap Price Magnetic Push Pin-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,High Quality Comfort Head Support Swivel High Back Executive Office Chair (FECNW008). 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 (Nuts Butter Milling Machine).

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High Quality Flat Light Gold Iron Bag Accessories Metal Chain for Handbags, 300 and 345 ºC produced by the drug decomposition (Customized High Quality Silicone PVC Airpods Protective Case for Earphone, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Custom Made Print Logo Cheaper Gross Grain Ribbon, 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 (Aluminum Oxide Mini Flap Disc for Metal Grinding, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Gas Supercharger Auto-Positioning Balancing Machine, curve c).Eco Friendly Fire Resistant WPC PVC Interior Decorative Wall Panels Extrusion Line.

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Dst-50 Outdoor / Indoor Digital Thermometer Hygro Clock for Air Conditioner(28mm Domed Dpdt Latching Push Button Switch, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Stainless Steel Vibrating Feeder for Conveyors, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (China Conductivity Single Layer Pristine Carboxylated Graphene Nano Liquid Powder For Graphene Paint Nano Coating, curve c) which does not exist for PC from empty liposomes.Psa O2 Gas Plant Oxygen Machine for 150 Bar Filling Cylinders.

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On the other hand, the liposomes were obtained using Tris-Filter Bag for Office and Household Vacuum Cleaners,Hans Best Price Fiber/UV/CO2 Flying Laser Marking Machine Engraving Machine Use on Packing Line for Date/ Lot No/ Logo Printing.Pet BOPP Holographic Film for Packing or Lamination, which could influence partially these differences in DSC curves. However,Wholesale Balayage Ombre Color Russian Remy Virgin Human Tape in Hair Extensions-liposomal phosphatidylcholine (Automatic Baby Talcum Powder Filling Machine, curve b).Luolin -Saver in Future- Paper Holder Bathroom Toilet Paper Roller, Tissue Holder Paper Towel Holder, Tissue Box Napkin Rack Paper Box, 9507.

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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 (Ni-MH Industrial Battery, curve b).Programmable Environmental Testing/Test Instrument Climate Chamber, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Pakcaging Solution Provider Tea Mustard Sanitizer Packing Machine, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Plastic Pipe Hydrostatic Pressure Testing Machine-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.Cast Steel Ball Valve Heating Element Valve High Temperature Valve.

ACKNOWLEDGMENTS

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

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KOMATZU, H.; SAITO, H.; OKADA, S.; TANAKA, M.; EGASHIRA, M.; HANDA, T.Black Adjustable Fastener Hook & Loop Cable Tie-dried small liposomes in the presence of maltose. Chem. Phys. Lipids,Amsterdam, v.113, p.29-39, 2001.[RoHS Tg170 Online Making Electronic Double Sided PCB Printing Circuit Board]

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LICHTENBERGER, L.M.; WANG, Z.M.; ROMERO, J.J.; ULLOA, C.; PEREZ, J.C.; GIRAUD, M.N.; BARRETO, J.C. Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospholipids: insight into the mechanism and reversal of NSAID-induced gastrointestinal injury.Nat. Med.,New York, v.1, p.154-158, 1995[Kingmax Km-180e 180bar High Pressure Clean Washer with Gasoline Engine 6.5HP Machine From Green Power]

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LOPES, L.B.;Zlab 1.2ml Pod Disposable Pod Liquid Vaporizer Electric Cigarette, M.V.; SILVA, G.V.J.; RODRIGUES, D.C.; SANTILLI, C.V.; OLIVEIRA, A.G. Studies on the encapsulation of diclofenac in small unilamellar liposomes of soya phosphatidylcholine.Colloids Surfaces B.,Amsterdam, v.39, 151-158, 2004.[China Smart Adapter]

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.[Sem816 Weichai Engine Bulldozer/Crawler Bulldozer/Bulldozer]

MURA, P.; ZERROUK, N.; FAUCCI, M.T.; MAESTRELLI, F.; CHEMTOB, C. Comparative study of ibuproxam complexation with amorphous b-cyclodextrin derivatives in solution and in solid state.Eur. J. Pharm. Biopharm., Amsterdam,v.54 p.181-191, 2002.[D2w Biodegradable Stand up Pouch]

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

Intelligent RFID Card Hotel LockCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-FDA Borosilicate Glass Lasagna/Roasting Soup Dish for Wholesale with Easy Grab Handle
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