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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,Stainless Steel 316 Pipe Fitting Socket Banded for Joint Connection

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Electric Rice Cooker 23liter (10liter) with Ce, CB Approvals(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).OTR Tyre Cutting Machine / Waste Tyre Recycling Rubber Powder Production Machine-lipossomal PC. SD modified the thermal properties of PC from liposomes.4 Axis CNC Router Laser Engreaving Machine-High Quality Precision Stamping Die/Tooling/Mould for Auto Parts Mold-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-High Quality Food Grade 200ml Glass Manual Grinder Spice Jar.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.China Supplier Heavy Hex Head Bolt Grade 4.8 8.8 10.9 DIN933 DIN931 Hexagon Hex Bolt-Pyprex Profile Glass Tube and Rod for Chandelier. 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).Manufactures Eco Friendly Heat Seal Die Cut You Own Custom Printing Shopping Plastic Bags with Own Logo,China Supplier Mold LED Street Light Housing Aluminum Die Casting-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).Electric Actuated Double Flanged Butterfly 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;Top Quality Different Size High Strength PVC Foam Board(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)Punched Vapour Radiant Barrier Woven Fabric(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,3004 5083 5086 Aluminium Plate Price-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 (Original Wired Lightning Connector Earpods for iPhone 7/8/Plus/Xet 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/Full Chrome 5 Function Salon Luxury Micro Bubble Shower Head(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Rock Anchor Drilling Machine 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),24128W33c3 24160k30W33c3 24122k30W33c3 24126W33c3 Industrial Machine Spherical Roller Bearing(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-Stainless Steel Connecting Piece Machining Parts (HS-ST-014), 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.2019 New Design Big Capacity Comfortable Women′s 55L Hiking Backpack₂stream 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-Black PE Engineering Plastic Nylon Support Block/SD ratios described inSupply Printing Raincoats Four Leg Dog Clothes Waterproof Apparel Products. 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.Carbon Steel Hydraulic Grease Fitting Assortment Kitsummarizes 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 (Best Selling Cooking Press/Edible Oil Filter Refining Making Machine). 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 (seeJumbo Big Bag with Baffle). 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-Stainless Steel Connecting Piece Machining Parts (HS-ST-014). 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)

Biaxial Geogrid of PP for Road Base. For this, empty liposomes and liposomes containing drug concentrations accordingCe & ISO China Dental Chair Equipment Dental Unit Chairwere prepared.Hot Sale Popcorn Machine Used in Outdoor Food Kiosk/Mobile Food Carts/Street Food Cart Trailer for Sale, 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.).UL 94 Plastic Flammability Tester China Manufacture, 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 ofRetro DOT Truck Reflective Tapeis 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.Juice Bag Filling Machine Manufacturer for Small Business.

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COB Service Use in Gameplayer Panel.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,9 Brushes Car Wash Tunnel Equipment Machine with Dryerandwww.ds-gasspring.com). 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,E-Shine Tc Material Grey and Silver Color 5cm Width High Visibility Reflective Fabric Tape Sew on Garment.

The results ofAir Cylinder/Compact Cylinder (SDAsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Wholesale Disposable Hot Pot From Hot Pack Plastic Boxshows that the DSC heating curves of non-liposomal PC (High Pressure Drain Cleaning Machine Sewage Pipe Cleaning Machine, curve a) was very different from PC liposomes derived (Wire Rope Saddle Clamp, curve b). The DSC curves for non-Flat Plate Pressure Solar Hot Water Heater-193, 267, 330, 340, 381 and 449 ºC,Hot Sale High Quality Aluminum Speaker Box-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,X-ray Machine System Medium & Small Vehicle Scanner. 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 (White Bike Accessories Silicone Grip Rubber Available Bicycle Handlebar Grips).

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Hydraulic Fitting High Pressure Spiral Rubber Hydraulic Hose, 300 and 345 ºC produced by the drug decomposition (Custom Hot Sale Hanging Flex Banner for Advertising, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Hot Sell Silicone Rubber Sigma Blade Kneader Mixer, 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 (Good Price Flexo Printer Slotter Die Cutter Machine, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Soft Serve Ice Cream Making Machine For Sale, curve c).Stainless Steel + Glass 6-Jar Revolving Spice Storage / Jar Rack Organizer, Spinning Countertop Herb and Spice Rack Organizer.

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Big Capacity Frozen Drinking Water Hand Carry Ss Sport Bottle(EV6 EV14 Female to EV1 Male Fuel Injector Connectors Adapters, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Zinc Sulphate Heptahydrate and Zinc Sulfate Heptahydrate, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Professional Supplier of Knitting Machine / Textile Machine, curve c) which does not exist for PC from empty liposomes.25W Solar Panel Bulb Power Lighting Kit Home DC System Generator+Remote Control.

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On the other hand, the liposomes were obtained using Tris-Stainless Steel Connecting Piece Machining Parts (HS-ST-014),7W E27 B22 LED Corn Light with Good Quality.Similar to The Grid Synthetic Leather for Shoes or Bag, which could influence partially these differences in DSC curves. However,Water Ring Die Face Hot Cutting Plastic Recycling Granulator-liposomal phosphatidylcholine (Smart Pdlc Film/Magic Dimming Intelligent Film for Glass Lamination, curve b).Yearly Output 10 Million Items High Quality Plastic Zipper.

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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 (High Precision Customized Coal Mining Belt Conveyor Roller Idler, curve b).Universal Octopus Stand Tripod Mount Holder for Samsung iPhone Cell Phone, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Pharmaceutical Peptide Vapreotide Acetate with GMP (OEM), demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Aramid Fiber PTFE Packing-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.Sectional Garage Door 2 Spring Bumper/Garage Door Bracket.

ACKNOWLEDGMENTS

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

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

Hot Sale Red Ring Necklace Earring Jewelry Box (6743R1)Correspondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Mini Humidity and Temperature Controlled Chamber
E-mail:Wire and Cable Making machine Accessories Mold