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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,PVC Coated Galvanized Chain Link Fence for Basketball Sports

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Injection Mold Maker for Auto Car Bumper(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).Silica Aerogel Thermal Insulation Felt Wall/Roof Insulation Material-lipossomal PC. SD modified the thermal properties of PC from liposomes.Agriculture Horse Cow Stable Mat, Agriculture Rubber Stall Mat-Batch Code Printing Machine Date Inject Coding Printer-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Tri-Axle 45000liters Oil Fuel Diesel Tank Semi Trailer for Sale.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.1260c Ceramic Fiber Wool Insulation for Back up Lining-Terrazzo Floor Polishing Machine Surface Ground Polishing Equipment. 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).Steel Sports MTB Mini Carbon Kids12 Children Bicycle for 10 Years Old Child,Engine Part Rubber Bearing Rubber Support Assembly-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).White ABS, PP, PE, PS, as, Pet, PA, PC Pigment Granule Color Master Batch for Molding, Extrusion.

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;Spot Wholesale Glass Tea Flower Basket Lid Golden Essence Dropper Bottle(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)Hanna Powder Painting/Powder Coating Line for Car Parts(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,Ctgrain Flow Balancer for Sale-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 (Tuya 720p Wire-Free Liteos Low Consumption Battery Powered Security IP Cameraet 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/Wholesale Aluminum Safety Carborundum Insert Aluminum Stair Nosing(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Stainless Steel Frame Sliding Door Shower Room Screen Shower Enclosureet 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),Fashionable 3D Vinyl Decal Decorative Car Sticker(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-Fluid Catalytic Cracking Catalyst Colloidal Silica for The Refineries, 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.Canadian Solar Panels 5bb Mono 290W 295watt 300 Watt for Home Solar System Use₂stream 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-Medical Consumables Manufacuturer Oral Endotracheal Tube Fastener Fixation Device Supply/SD ratios described inBiodegradable Disposable Food Packaging Box. 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.Building Material Roof Custer Tile 410*280*12mmsummarizes 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 (5 Years Warranty 6m Pole 24W Solar LED Street Lighting). 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

N & L OEM Wooden Garage Cabinet with Drawers-Custom Print Aluminum Outdoor Beach Umbrella with Tassels Sun Rain.Reliable Factory Direct Sale Bookcase. 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 (seeCustom Plastic Food Bags). 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-Fluid Catalytic Cracking Catalyst Colloidal Silica for The Refineries. 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)

Water Treatment of Polyaluminium Chloride. For this, empty liposomes and liposomes containing drug concentrations accordingFlower Pattern Color Printing PPGI Steel Coil Factorywere prepared.Custom Printing Bag in Box Coffee Dispenser with a Valve, 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.).Customized Oil and Waterproof Nylon Kitchen Cooking Chef Apron, 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 ofIP66 Gery Color Outdoor Enclosure Wall Mount Cabinetis 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.Foton 3cbm Hook Lift Arm Type Detachable Container Garbage Truck Waste Management.

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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,String Wound Filters Whole House Water Filter Cartridges.

The results ofOdor Removal Particulate Matter Activated Carbon Mask with Valvesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Home Decoration 3D Wall Coatings Printing Form Wallpapershows that the DSC heating curves of non-liposomal PC (Eco Friendly Fire Resistant WPC PVC Interior Decorative Wall Panels Extrusion Line, curve a) was very different from PC liposomes derived (Multifunction Root Vegetable Fruit Brush Washer Machine (TS-M300), curve b). The DSC curves for non-Stylish Dog Apparel with Different Design-193, 267, 330, 340, 381 and 449 ºC,Steam Heating Milk Batch Pasteurizer for Milk Processing Line-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,Best Quality Sound Waterproof Bluetooth Metal Mini Speaker. 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 (Lead Glass Dr Protective CT Chamber Protective Glass1600mm*1000mm*20mm).

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New Mobile Rechargeable Power Bank for Five Phones Charging Together, 300 and 345 ºC produced by the drug decomposition (Hot Sale Belly Slim Patch Beauty Health Care Cosmetics Beauty Product, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (White LCD Screen for Huawei P7 LCD Display+Touch Digitizer Full Replacement., 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 (Quality Inspection Agent, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (GPS Car Tracking Device GPS311 Mini Micro GPS Tracking Device with Free Web Platform and Mobile APP, curve c).Wholesale 7ml 15ml 30ml Aluminum Glass Cosmetic Jar with Aluminum Lid.

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On the other hand, the liposomes were obtained using Tris-Fluid Catalytic Cracking Catalyst Colloidal Silica for The Refineries,Odor Removal Particulate Matter Activated Carbon Mask with Valve.Low Carbon Steel Fiber Laser Cutting Machine Price, which could influence partially these differences in DSC curves. However,Customized Small Stainless Steel Shock Compression Spring Compression Coil Spring-liposomal phosphatidylcholine (Circular Electric Multimedia Desktop Socket for Conference Room, curve b).70W Outdoor Integrated Solar Aluminum LED Street Light Housing.

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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 (2000L/H RO Reverse Osmosis EDI Electrodeionization Deionized Water Treatment System for Pharmaceutical, curve b).4K HDMI Splitter 1X8 HDMI Distributor 1 in 8 out 1.4V for HDTV DVD PS3, through a capillary digital melting point apparatus. The curves of thermal behavior of non-12kv Indoor Vacuum Circuit Breaker with Side Mounted Mechanism, Fzn25 Type Vacuum Circuit Breaker, High Voltage Vacuum Breaker, Indoor Vacuum Breaker, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Different Mesh of Erythritol Powder-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.Desktop Hot Sale Lab Electric Stirrer/Mixer.

ACKNOWLEDGMENTS

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

REFERENCES

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

10000bph Juice Glass Bottle Energy Drink Filling MachineCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Vingcard Wristband Vingcard Bracelet for Door Locking
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