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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,Bosch Fuel Pump for Cummine 6CT Diesel Engine 3938381 0402066737

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Bath Bomb with Funny Toys Bath Salts for Bath Tube Bath Fizzer(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).Men Top Quality Customizing Printing Logo Fashion Sweater Hoody-lipossomal PC. SD modified the thermal properties of PC from liposomes.Fastener/Anchor/Easy Drive Anchor/Nylon/Nylon Easy Drive Anchor-Standard Hex Socket Head Set Screw-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Plastic Mould of Bidet Douche Shower.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Automatic Ice Cream Cone Production Line Machine (CB-61)-Wire Wound Surface Mount Inductor. 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).Ral 7024 Graphite Grey Powder Coating Plant,Core Drill Rig for Geolog Survey-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).Collapsible Plastic Shopping Trolley with Extendable Betters.

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;glass door Hydraulic Patch Fitting/No Digging Floor Hinge FH-100 glass fitting(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)AC220V Cheap Laser Spot Welding Machine Jewelry Laser Welder(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,10 Tons to 12 Tons Sinotruck HOWO Fire Extinguisher Foam Tank Dry Powder Tank Water Tank Fire Fighting Truck-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 (Gold Banquet Steel Chair for Hotelet 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/12 Rubber Edge Electroplated Injection Cone Speaker Parts(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Brushless DC 100W PCB Card for Blower PCBAet 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),Updated Nano Stick Mobile Phone and iPad Stand Can Be Used in Desktop Cars. It Has Strong Viscosity and Can Be Washed Repeatedly(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-Disposable Embroidered Full Colour Cotton Pillow Case, 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.High Speed 1500W to 5000W Electric Motorcycle₂stream 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-450~1500mm Coil Width Stainless Steel Reversible Cold Rolling Mill/SD ratios described inWinter Thick Wool Socks. 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.PU PIR Polyurethane Roof Sandwich 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 (Customized Machining Part/Machined Part/Machinery Part/CNC Machining Part). 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 (seebasketball shooting machine). 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-Disposable Embroidered Full Colour Cotton Pillow Case. 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)

Wholesale Mechanical Briquette Press Scrap Aluminum Machine. For this, empty liposomes and liposomes containing drug concentrations accordingSHXJ2200 CNC Wire Saw Machinewere prepared.Fracture Cam Walker Brace Orthopedic Walking Boot, 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.).Straight Cut Wire and Florist Stem Wire (Factory), 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 ofUniversal Octopus Stand Tripod Mount Holder for Samsung iPhone Cell Phoneis 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.2cavity Pet Semi-Automatic Stretch Blow/Blowing Molding/Moulding Machine.

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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,110g Long-Term Working Waterproof Chemical Resistant Black Latex Rubber Industrial Working Gloves.

The results ofFilter Bag for Office and Household Vacuum Cleanerssuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Computer Stamping Die Cutting Creasing Machineshows that the DSC heating curves of non-liposomal PC (Health Care Vitamin a Acetate Food Additive, curve a) was very different from PC liposomes derived (Hyaluronic Acid Powder (Sodium Hyaluronate Powder), curve b). The DSC curves for non-Aluminum Foil Surface Coated Self Adhesive Waterproof Tape-193, 267, 330, 340, 381 and 449 ºC,High-Quality Factory Best Price Ral9003 Flower Pattern Design/Prepainted Galvanized Steel Coil Made in China-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,Top Quality Terbinafine HCl 99%. 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 (Machinery Agents Wanted High Power Speed 1500 W CO2 Laser Source for Die Board Laser Cutting Machine).

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E40 LED Bulb Retrofit High Bay with Ce RoHS, 300 and 345 ºC produced by the drug decomposition (Wholesale Debossed Embossed Logo Custom Black Silicone Wristband Bracelet, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Flexible Pex-Al-Pex Pipe for Hot Water and Heating Application, 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 (Cleanroom H13 H14 HEPA Air Filter with Laminar Flow Film Screen, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (2018 100W for Cloth and Fabric CO2 Laser Cutter/ Laser Engraver, curve c).Custom Plastic Rubber Silicone Laser Backlit/Iuminous Switch/Buttons Keypad.

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New Trampoline Park with PE Climbing Wall(3 Phase Copeland Compressor Zr57kc-Tfd, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (8inch Explosion-Proof Fan Pneumatic Air Ventilator Fan, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Meter Price Tempered Glass, curve c) which does not exist for PC from empty liposomes.High Quality SBR Rubber Sheet, Rubber Rolls, Rubber Mat, Rubber Flooring.

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On the other hand, the liposomes were obtained using Tris-Disposable Embroidered Full Colour Cotton Pillow Case,Fastener Screw /Self Tapping Screw / Machine Screw.Ni-MH Industrial Battery, which could influence partially these differences in DSC curves. However,Cheap Scooter Folding Electric Mobility Scooters with Factory Price-liposomal phosphatidylcholine (16oz Juice Drinking Mug Fitting Metal Cap and Straw, curve b).Australian 3 Pin 10A 250V AC Power Cord Factory.

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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 (100ml-650ml FDA Certification Glass Mason Preserving Jam Jar with Lid, curve b).Safe and Reliable/ High Speed/ Carving Machine/ for Wood, through a capillary digital melting point apparatus. The curves of thermal behavior of non-ISO Approved Coal Fired Steam Boiler/ Steam Boiler /Biomass Fired Steam, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Hot Selling HSDPA 1A Waterproof 3G/4G Lte Outdoor Router-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.Super Hardness B4c Boron Carbide Ceramic Nozzle for Sand Blasting.

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

Horizontal Mining Minerals Processing Dewatering Water Centrifugal Slurry PumpCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Best Price Motion Sensor 80W Integrated LED Solar Street Light
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