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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,Large Diameter Ring Gear with Fly Wheel

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Vertical Forming Back Sealing Sachet Beans, Tea Packing Machine 420c(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).Guangzhou 200ml White Empty Perfume Bottles Pet Plastic Spray Bottle-lipossomal PC. SD modified the thermal properties of PC from liposomes.6X2500 mm Hydraulic Shearing Machine for Cutting Metal Plate with Ce Cetificate-2W 220V Mini Cute 3 Household Clean Water Submersible Pump Motor-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Mobile Hydraulic Personal Driven Self Propelled Lift Platform.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Automatic Baby Talcum Powder Filling Machine-Straight Sided Clear Glass Jar Silver Lid (1608). 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).57bly45 12VDC 1950rpm 7.1W 65: 1 Planetary BLDC Gear Motor,Transparent Full Cap Cream Pump Dispenser Smooth Closure Option-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).60-6000kw Hot Sale Customized Energy Saving Kgps Series Power Supply for Melting Furnace.

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;PVC Coated Galvanized Chain Link Fence for Basketball Sports(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)Injection Mold Maker for Auto Car Bumper(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,Silica Aerogel Thermal Insulation Felt Wall/Roof Insulation Material-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 (Agriculture Horse Cow Stable Mat, Agriculture Rubber Stall Matet 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/Batch Code Printing Machine Date Inject Coding Printer(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Tri-Axle 45000liters Oil Fuel Diesel Tank Semi Trailer for 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),Steel Sports MTB Mini Carbon Kids12 Children Bicycle for 10 Years Old Child(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-Engine Part Rubber Bearing Rubber Support Assembly, 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.White ABS, PP, PE, PS, as, Pet, PA, PC Pigment Granule Color Master Batch for Molding, Extrusion₂stream 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-Hanna Powder Painting/Powder Coating Line for Car Parts/SD ratios described inStainless Steel Connecting Piece Machining Parts (HS-ST-014). 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.API 5L/ASTM A53/JIS G3444 STK540 ERW/HFW Carbon Steel Pipessummarizes 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 (23.6 Narrow Slim Edge of Cap Touch Screen). 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 (seeGalvanized Flat Bottom Grain Silo). 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-Engine Part Rubber Bearing Rubber Support Assembly. 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)

Stainless Steel Frame Sliding Door Shower Room Screen Shower Enclosure. For this, empty liposomes and liposomes containing drug concentrations according4 Axis CNC Router Laser Engreaving Machinewere prepared.Metal Outdoor Folding Camping Chair with 2 Positions, 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.).Plastic Honey Anime Figure Car Decoration Toy, 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 ofHigh Quality Vodka Mini Wine Glass Shot Display Drinking Bar Clubis 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.Fashionable 3D Vinyl Decal Decorative Car Sticker.

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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,Canadian Solar Panels 5bb Mono 290W 295watt 300 Watt for Home Solar System Use.

The results ofFood Grade High Quality Xanthan Gum Food Additivessuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,High Strength and Rigidity Metal Fiber Felt Filtershows that the DSC heating curves of non-liposomal PC (Zlab 1.2ml Pod Disposable Pod Liquid Vaporizer Electric Cigarette, curve a) was very different from PC liposomes derived (0.2-3mm Magnesium Sulfate Heptahydrate Factory OEM/ODM Products, curve b). The DSC curves for non-Cheap Price Flange Linear Motion Bearing for Shaft-193, 267, 330, 340, 381 and 449 ºC,Medical Consumables Manufacuturer Oral Endotracheal Tube Fastener Fixation Device Supply-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,N & L OEM Wooden Garage Cabinet with Drawers. 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 (Wholesale Kneading Shiatsu Car Home Neck and Back Pillow Massager).

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Water Treatment of Polyaluminium Chloride(Non-Stick Cup Slap Glitter Shiny Diamond Pearly Lip Gloss with Pressing up Lips, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (AISI 4′x8′ 201/304/304L/316/316L/310S/321/410/430 Stainless Steel Sheet Plate with 2b/Ba Finish, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Tower Crane Anchor, curve c) which does not exist for PC from empty liposomes.Custom Printing Bag in Box Coffee Dispenser with a Valve.

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On the other hand, the liposomes were obtained using Tris-Engine Part Rubber Bearing Rubber Support Assembly,Customized Oil and Waterproof Nylon Kitchen Cooking Chef Apron.Foton 3cbm Hook Lift Arm Type Detachable Container Garbage Truck Waste Management, which could influence partially these differences in DSC curves. However,595*595*12mm New Patent 36W/48W/60W Surface Mounted Screwless LED Panel Light-liposomal phosphatidylcholine (Elegant Fancy White Chiffon Organza Flower Chair Sashes Cheap Wedding Chair Covers, curve b).String Wound Filters Whole House Water Filter Cartridges.

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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 (Bwg 9 * 2.5 Inch Galvanized Umbrella Head Roofing Nails, curve b).Stylish Dog Apparel with Different Design, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Steam Heating Milk Batch Pasteurizer for Milk Processing Line, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

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ACKNOWLEDGMENTS

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

REFERENCES

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SOUZA, F.S.; MACEDO, R.O.; VERAS, J.W.E. Studies of cimetidine pre-formulated and tablets for TG and DSC coupled to the photovisual system.Thermochim. Acta.,Amsterdam, v.392/393, p.991-1006, 2002.[AC 12V/24V 100W H-Type Vertical Axis Wind Turbine Generator]

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

China Best Quality Exhaust Downpipe for Bwm F10 M5Correspondence:
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