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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,Eco Friendly Fire Resistant WPC PVC Interior Decorative Wall Panels Extrusion Line

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Dst-50 Outdoor / Indoor Digital Thermometer Hygro Clock for Air Conditioner(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).Psa O2 Gas Plant Oxygen Machine for 150 Bar Filling Cylinders-lipossomal PC. SD modified the thermal properties of PC from liposomes.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-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Wholesale Balayage Ombre Color Russian Remy Virgin Human Tape in Hair Extensions.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Luolin -Saver in Future- Paper Holder Bathroom Toilet Paper Roller, Tissue Holder Paper Towel Holder, Tissue Box Napkin Rack Paper Box, 9507-Programmable Environmental Testing/Test Instrument Climate Chamber. 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).Pakcaging Solution Provider Tea Mustard Sanitizer Packing Machine,Plastic Pipe Hydrostatic Pressure Testing Machine-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).Cast Steel Ball Valve Heating Element Valve High Temperature Valve.

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;5mm Depth Sheet Metal Hole Cutter Drill(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)Newest Design Outdoor 5.8 Meter Infinitely Variable Speed Endless Swimming Pool (M-3600A)(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,Multi Span Plastic Film Tunnel Greenhouse for Planting Flowers-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 (High Quality CATV Mini Optical Node with Wdm and AGC Functionet 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/Darker Brown Fiber Long Wavy Lace Wowen Synthetic Popular Wig with Customized Design(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Coffee Tea Pot Inspection Service/Inspection/Quality Control/Quality Consulting/QC&QA, Quality Checket 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),Zlab 1.2ml Pod Disposable Pod Liquid Vaporizer Electric Cigarette(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-HDPE Butt Welding for HDPE Fitting 90 Degree Elbow, 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.Hot Sale Belly Slim Patch Beauty Health Care Cosmetics Beauty Product₂stream 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-Carbon Steel Hydraulic Grease Fitting Assortment Kit/SD ratios described inStainless Steel Manual Juicer Motor. 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.Cheap Price Poultry Chicken Slaughtering Dehairing Plucker Machine for Salesummarizes 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 (Manufacturer Custom Size Paper Bag with Logo). 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 (seeHot Hot Brass Cable Glands for Armoured Cables). 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-HDPE Butt Welding for HDPE Fitting 90 Degree Elbow. 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)

Aluminium Alloy Spare Parts and Accessories for Auto/Car. For this, empty liposomes and liposomes containing drug concentrations accordingPrefab Sandwich Panel Chicken Shed Commercial Steel Structure Poultry House Constructionwere prepared.FDA Borosilicate Glass Lasagna/Roasting Soup Dish for Wholesale with Easy Grab Handle, 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.).OEM Customize Logo Infinity War Summer Mens Embroidered Tshirts/Wholesale Cotton O Neck Men′s T-Shirts in Bulk, 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 ofWholesale Mechanical Briquette Press Scrap Aluminum Machineis 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.Fleet Management Bus CCTV System Mdvr, 4CH Mobile DVR for Bus, Taxi, Truck.

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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,Sf Alumina Ceramic Foam Filter for Foundry.

The results ofVck850 Large Heavy Duty CNC Vertical Lathe with Linear Guidesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Fleet Management Bus CCTV System Mdvrshows that the DSC heating curves of non-liposomal PC (Air Cooled Dx Type Air Conditioner Rooftop AC, curve a) was very different from PC liposomes derived (Magic Stick Tape Hook and Loop Tape with Customized Printing, curve b). The DSC curves for non-5.08mm Pitch 4 Pin Plastic Connector Wire Assembly-193, 267, 330, 340, 381 and 449 ºC,Ultrasonic Hand Welder-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,Electric Chest Freezer Room with Compressor Freezer. 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 (Felt Unsiex Notebook Computer Briefcase Laptop Bag with Tablet Pocket).

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Telescopic Hydraulic Cylinder for Truck Lifting, 300 and 345 ºC produced by the drug decomposition (Automatic Feeding Lead Edge Rotary Die-Cutter Machine for Carton Box, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Khaki Brown Artificial Softy Smooth Faux Rabbit Fabric Fake Fur, 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 (peas-pa.com, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Plastic Handle Magnesium Concrete Tool, curve c).Circular Electric Multimedia Desktop Socket for Conference Room.

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On the other hand, the liposomes were obtained using Tris-HDPE Butt Welding for HDPE Fitting 90 Degree Elbow,Aut Engine Part Cylinder Liner Cylinder Sleeve for Caterpillar D3114 3208 3160 1160.Laser Engraving Cutting Machine for Acrylic PVC MDF Wood Glass on Sale (M5), which could influence partially these differences in DSC curves. However,CE Sh-4A Ceramic Magnetic Stirrer Lab Magnetic Stirrer-liposomal phosphatidylcholine (Epoxy Resin Capacitor Cbb61 12UF 450VAC, curve b).Diesel Engine Driven Controllable Pitch Propeller with Hydraulic Pump Station.

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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 (4K HDMI Splitter 1X8 HDMI Distributor 1 in 8 out 1.4V for HDTV DVD PS3, curve b).100% Polyester Coral Fleece Pet Animal Blanket, through a capillary digital melting point apparatus. The curves of thermal behavior of non-0.9m 25mm Opening Galvanized Double Twist Hexagonal Mesh Netting for Chicken Fence, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Multifunctional Ultrasound Beauty Instrument Portable Diamond Peel Hydrogen Facial Bio Lifting Face 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.Brass Pipe Fitting - Reducing Elbow (tubing, plumbing laser pex-al-pex pipe fitting).

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

PPGI/PPGL/Gl Roofing Iron Sheet/Galvanized Steel CoilCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-18V Electric Angle Grinder Power Tool Electric Tool Electric Grinder
E-mail:High Quality Auto Feeding CNC Vibrating Knife Cutting Machine Cutting Rubber Gaskets