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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,China High Quality Rectangular Aluminum Mesh Plate for Outdoor Use

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,PPGI/PPGL/Gl Roofing Iron Sheet/Galvanized Steel Coil(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).High Power Single Burner Electric Induction Cookware Set-lipossomal PC. SD modified the thermal properties of PC from liposomes.Water Hyacinth Reed Cutter Aquatic Weed Harvester Cutting Ship /Rubbish Collection Cleaning Boat Vessel Trash Skimmer Water Clean Machine in Lake River Dam-Set of 8 New Iridium Spark Plugs # 12625058 Acdelco Professional # 41-103-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Geodetic GPS Receiver for Land Surveying GPS Gnss Rover Base with UHF Radio.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Original Memory Card Ultra SD Card Micro SD Card Class 10 Memory Card 16GB-Sg6.2g/cm3 Ceria Zirconium Grinding Beads 2.4-2.6mm. 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).Flexible Keyboard PCB Inverter Welding PCB Board PCB Components,Cheap Price Poultry Chicken Slaughtering Dehairing Plucker Machine for Sale-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).Prefabricated Steel Structure Warehouse (BYSS-121).

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;High Quality Billiard Pool Table(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)Prefab Sandwich Panel Chicken Shed Commercial Steel Structure Poultry House Construction(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,Custom Services Aluminum Forging Metal Spare Parts-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 (Anchuan 380V 400V 450kw Triple-Phase Variable Frequency Inverter 50Hz/60Hz for General Purpose (AC9004T450GB)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/High Brightness Outdoor Full Color LED Sign LED Display Board(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Plants/Warehouse Using Small Jib Crane 1000kgset al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

China HOWO A7 Tractor Trailer Head Truck for Sale. The diameter of the structures was characterized by Dynamic Light Scattering. The amorphous product derived from lyophilization was analyzed by DSC in order to verify the differences in the properties of PC,Trichoderma Harzianum Como Promotor De Crecimiento.

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),Competitive Quality Aluminum Silicon Flux-Cored Rods/Rings/Wires(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-A4 T Shirt Transfer Paper for Light Color, 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.PPM-T314A Pressure Transmitter 4-20mA for Internal Combustion Engine from China₂stream 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.

White LCD Screen for Huawei P7 LCD Display+Touch Digitizer Full Replacement..6 mM (40 mg/mL) was prepared in ethanol. 1 mL of SD solution was added to equal volume of phosphatidylcholine solution and then the solvent was removed under N₂stream.

The dry lipid films with and without drug were hydrated at 25 ºC room controlled temperature for 45 min with 4 mL of Tris-Dust Sweeper Floor Easy Flat Mop/SD ratios described inPrecision Standard Steel Tablet Press Punch Die Set. 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.COB Service Use in Gameplayer Panelsummarizes 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 (High Quality Plastic Green Masterbatch Color for PP PE). 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 (see30% Silver Brazing Welding Rod Copper-Zinc Wire TIG Rod). 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-A4 T Shirt Transfer Paper for Light Color. 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)

Portable Android PDA with Fingerprint Reader 1d/2D Honeywell Bar-Code Scanner. For this, empty liposomes and liposomes containing drug concentrations according Acrylic Knitted Scarf Jacquard Football Scarfwere prepared.Precision Customized Hexagonal Nut, 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.).6061-T6 Aluminium Profile System Extrusion Profiles with Powder Coating, 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 ofTk-Jc2104 Caster Wheel for Sliding Door Wholesaleis 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.China Brand 3 Axle 12 Wheels Rear Dump Tipper Hydraulic Lifting Tipping Dump Full Trailer.

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Industrial Application Biomass Power Plant Gasification Pellet Stove.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,2019 Hot Circular Vibrating Screen MachineandRF Electrosurgical Unit Electrodes for Cutting). 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,Yoga / Sports Blank Custom Fitness Leggings.

The results ofCustomize Polypropylene Hollow Sheet PP Waterproof Boardsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Aqualand 14feet 4.3m Foldable Inflatable Fishing Boat/Sports Motor Boat (aql-425)shows that the DSC heating curves of non-liposomal PC (2019 Hot Selling Decorate/Home Furnishing Tool Stone/Brick Lifting, curve a) was very different from PC liposomes derived (50W Plastic Bottle Series Number Printing Fiber Laser Engraving Machine, curve b). The DSC curves for non-Length Customed BOPP Tape for Packing-193, 267, 330, 340, 381 and 449 ºC,Computer Stamping Die Cutting Creasing Machine-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,Stainless Steel Shampoo Mixing Tank /Ointment Vacuum Emulsifying Machine. 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 (Factory OEM New Designer Leather Fashion Tote Bag Lady Handbag).

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Agricultural 25kg 50kg High Quality White Polypropylene Seed Woven Sack PP, 300 and 345 ºC produced by the drug decomposition (Mitered Corner Aluminum Poster Profile Snap Photo Frame, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (High Quality Automobile Cable Use Double Sided Reflective Aluminium Foil, 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 (Pan Mixer Type Concrete Batching Plant, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (32 Oz Food Container Rectangular Meal Preparation Bento Box with Lid, curve c).985b Medium Back Leather Boss Chair.

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Multiple-Layers Plasitc Pesticide Bottle Extrusion Blow Moulding Machine(Factory Price Interior & Exterior Use Aluminum Honeycomb Ceiling Panel Soundproof, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Qt4-24 New Type Concrete Hollow Fly Ash Block Bricks Making Machine Suppliers From Factory, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Car Armrest Seat Boxes, curve c) which does not exist for PC from empty liposomes.Perfect Homes Furniture 6 Seater Beige Rubber Wood Dining Table.

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On the other hand, the liposomes were obtained using Tris-A4 T Shirt Transfer Paper for Light Color,Chain Grate Stoker 10 Ton Coal Wood Fired Steam Industrial Boiler Price.Cable Entry Single Screw Terminal Block Wire Male Female Connectors, which could influence partially these differences in DSC curves. However,Factory OEM New Designer Leather Fashion Tote Bag Lady Handbag-liposomal phosphatidylcholine (Square Steel Ceiling Support Pipe Forming Machine, curve b).Freezer Room Sliding Door with Heat Wire.

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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 (WiFi Smart Light Switch DIY Breaker Module Tuya APP Remote Control Working with Alexa Echo, curve b).AC 12V/24V 100W H-Type Vertical Axis Wind Turbine Generator, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Power Metal Shear Machine Briquette Sheet Metal Big Square Baler Press, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Gi Steel Grating, Gi Bar Grating-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.Machinery Agents Wanted High Power Speed 1500 W CO2 Laser Source for Die Board Laser Cutting Machine.

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.[Stainless Steel 316 Pipe Fitting Socket Banded for Joint Connection]

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240V 4500W Industrial Immersion Tubular Heater Water Heater Heating Element, E.C.A.; TALSMA, H.; CROMMELIN, D.J.A.Rsm-DCT (D) Core Hole Borehole TV Test-dried liposome-carbohydrate mixtures with modulated temperature differential scanning calorimetry.J. Pharm. Sci.,Washington, v.87, p.231-237, 1998.[G550 Full Hard Aluzinc Steel / Anti Finger Galvalume Coils]

240V 4500W Industrial Immersion Tubular Heater Water Heater Heating Element, E.C.A.; ZHANG, W.; CROMMELIN, D.J.A.7inch Heavy Duty 24V CCD Bus/Truck Rear View Camera System Kit-FRP GRP Round Tube, Fiberglass Product Tube, FRP Pipe.Pharm. Res.,Arlington, v.9, p.1151-1160, 1997.[High Quality 16-32mm Soft Pipe for Washing Car]

VENEMA, F.R., WERINGA, W.D. The interactions of phospholipid vesicles with some anti-inflammatory agents.J. Colloid Interface Sci.,Amsterdam, v.125, p.484-492, 1987.[Super Fine Nanometer Sand Mill Bead Mill]

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

St00118 Sinotruk HOWO Heavy Duty 6X4 Tractor Truck 420HP -Non Used Mini FAW Isuzu Beiben Foton Pick up Cargo Vehicle Tipper Dump Dumper Van MachineCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Customized High Quality Silicone PVC Airpods Protective Case for Earphone
E-mail:Simulated Sand and Dust Test Chamber