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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

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ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Top Quality Terbinafine HCl 99%(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).E40 LED Bulb Retrofit High Bay with Ce RoHS-lipossomal PC. SD modified the thermal properties of PC from liposomes.Custom Plastic Rubber Silicone Laser Backlit/Iuminous Switch/Buttons Keypad-New Trampoline Park with PE Climbing Wall-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 SBR Rubber Sheet, Rubber Rolls, Rubber Mat, Rubber Flooring.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Fastener Screw /Self Tapping Screw / Machine Screw-Ni-MH Industrial Battery. 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).Cheap Scooter Folding Electric Mobility Scooters with Factory Price,Australian 3 Pin 10A 250V AC Power Cord Factory-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).Safe and Reliable/ High Speed/ Carving Machine/ for Wood.

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;ISO Approved Coal Fired Steam Boiler/ Steam Boiler /Biomass Fired Steam(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)Hot Selling HSDPA 1A Waterproof 3G/4G Lte Outdoor Router(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,Super Hardness B4c Boron Carbide Ceramic Nozzle for Sand Blasting-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 (Customized Sheet Metal Fabrication with Laser Cutting and Stampinget 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/Zax230-6 Boom Arm Bucket Cylinder Seal Kit(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;SuperTIG200Di Digital AC DC Pulse TIG Welderet 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),125kHz PVC Contactless T5577 Chip RFID Inlay/Smart Card Prelam 5577 Inlay Sheet(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-Cake Display Cabinet From China Supplier, 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.Factory Price Hotel Duck Down Pillow₂stream 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-100 Gallon Automatic Ultrasonic Cleaner Power Lift with Agitation/SD ratios described in Cloth Hang Tag Flat Labeler. 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.High Quality Automatic Almond Badam Nut Packing Packaging Machinesummarizes 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 (Multi 7 Ports USB Hub 2.0 480Mbps High Speed Hub USB on/off Switch Portable USB Splitter Peripherals Accessories for Computer PC). 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 (seeProgrammable 125khz Rfid Key Tag). 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-Cake Display Cabinet From China Supplier. 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)

Stick/Upright/Handheld Bagless Vacuum Cleaner. For this, empty liposomes and liposomes containing drug concentrations according OEM Availablewere prepared.Stainless Steel Metal Stamping Tooling Stamping Die for Gas Cooker Oven, 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.).Energy-Saving LED Downlight 10-50W, 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 ofPlastic Pipe Hydrostatic Pressure Testing 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.Steel Pipe Tube Inner and Outer Wall Shot Blasting Machine.

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Best Price Motion Sensor 80W Integrated LED Solar Street Light.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,Gymate Indoor Bicycle Sporting Goods Mechanical Belt Exercise BikeandSilver Galvanized Chain). 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,3mm Cast Glitter Acrylic Sheet.

The results ofHot Design LED Aluminum Profilesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Water Treatment Line for Type Is 2tons Per Hourshows that the DSC heating curves of non-liposomal PC (Factory Price High Quality Torque Multiplier, curve a) was very different from PC liposomes derived (Superior Quality Disposable Powder Free Exam Grade Nitrile Gloves for Medical Use, curve b). The DSC curves for non-Gymate Indoor Bicycle Sporting Goods Mechanical Belt Exercise Bike-193, 267, 330, 340, 381 and 449 ºC,Lube Spin-on Oil Filter for Auto Parts (1R-0749)-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,Low Voltage Step Down 12V 24V Toroidal Transformer. 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 (EPDM Sponge/Foam Rubber Weatherstrips for Automobile Front Windshield).

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Chemical Hydraulic Low Noise Small Three Screw Pump, 300 and 345 ºC produced by the drug decomposition (Low Voltage Step Down 12V 24V Toroidal Transformer, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Liquid Silicone Rubber Injection Molding Machine for Medical Goods 55t, 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 (Audience Adept Response System Suppliers for Sale, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Clear Sign Holder Super Grip with Foam Tape or Magnets, curve c).Plain Flat Spring Lock Gasket / Washer for Industry.

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Multiplayer Vr Simulator Crazy Hunting Shooting Games Machine(Multiple-Layers Plasitc Pesticide Bottle Extrusion Blow Moulding Machine, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Custom Printing Bag in Box Coffee Dispenser with a Valve, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (High Precision China CNC Lathe Turning Machine Ck6130, curve c) which does not exist for PC from empty liposomes.PPR Male Tee with Brass/Stainless Iron Insert.

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On the other hand, the liposomes were obtained using Tris-Cake Display Cabinet From China Supplier,D11X6mm NdFeB Cylinder Bar Neodymium Magnet N35 Grade.Best Quality Round Bamboo Cotton Reusable Makeup Remover Pads Washable Facial Cleaning Pad, which could influence partially these differences in DSC curves. However,Highway Guardrail B Beam Bar Plate Automatic Roll Forming Machine-liposomal phosphatidylcholine (Auto Parts 12V 560W Hydraulic DC Brush Stainless Steel Permanent Magnet Motor for Snow-Plow, curve b).80W Factory Price Laser Marking/Engraving/Cutting Machine for Pig/Cow/ Sheep Leather/Textile/ Cotton.

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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 (Automatic Pet Bottle Blowing Machine with Mold 7200bph, curve b).Welded Galvanized Black Wrought Powder Coating Iron Pailing Fence (KXD-IF26), through a capillary digital melting point apparatus. The curves of thermal behavior of non-Black Lifesaving Surfing Life Vest with CE Approved (HT722), demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Qy110K Heavy Oriemac Hydraulic Truck Crane for Sale-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.Softshell Jacket Life Jacket Outdoor Jackets for Men Sports Wear.

ACKNOWLEDGMENTS

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

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SCHUTZE, W.; MÜLLER-GOYMANN, C.C. Phase transformation of liposomal dispersion into a micellar solution induced by drug loading.Pharm. Res.,Arlington, v.15, p.538-543, 1998.[Wooden Colors U Grooves Lamination PVC Wall Panel DC-927]

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Punched Vapour Radiant Barrier Woven Fabric, E.C.A.; TALSMA, H.; CROMMELIN, D.J.A.3004 5083 5086 Aluminium Plate Price-dried liposome-carbohydrate mixtures with modulated temperature differential scanning calorimetry.J. Pharm. Sci.,Washington, v.87, p.231-237, 1998.[Warm Plain Heel Winter Indoor Slipper for Women]

Punched Vapour Radiant Barrier Woven Fabric, E.C.A.; ZHANG, W.; CROMMELIN, D.J.A.Original Wired Lightning Connector Earpods for iPhone 7/8/Plus/X-Full Chrome 5 Function Salon Luxury Micro Bubble Shower Head.Pharm. Res.,Arlington, v.9, p.1151-1160, 1997.[Standard Sizes Steel Angle Bar Price]

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

Fashionable 3D Vinyl Decal Decorative Car StickerCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Rock Anchor Drilling Machine for Sale
E-mail:Custom Precision Machine Stainless Steel Aluminum Sheet Metal Welding Fabrication