ORIGINAL PAPERS

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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,Safe and Reliable/ High Speed/ Carving Machine/ for Wood

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,ISO Approved Coal Fired Steam Boiler/ Steam Boiler /Biomass Fired Steam(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).Hot Selling HSDPA 1A Waterproof 3G/4G Lte Outdoor Router-lipossomal PC. SD modified the thermal properties of PC from liposomes.Super Hardness B4c Boron Carbide Ceramic Nozzle for Sand Blasting-Customized Sheet Metal Fabrication with Laser Cutting and Stamping-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Zax230-6 Boom Arm Bucket Cylinder Seal Kit.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.SuperTIG200Di Digital AC DC Pulse TIG Welder-Hot Sale Dermal Filler Lip Injection Hyaluronic Acid Lip Filler with Lidocaine. 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).Purple Household Stainless Steel Electric Kettle 1.8L,125kHz PVC Contactless T5577 Chip RFID Inlay/Smart Card Prelam 5577 Inlay Sheet-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).Cake Display Cabinet From China Supplier.

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;Factory Price Hotel Duck Down Pillow(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)Txk 1 Ton Crane Scale for Material Handling(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,100 Gallon Automatic Ultrasonic Cleaner Power Lift with Agitation-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 (New Tws Bluetooth Wireless Earbuds Stereo Headset for Saleet 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/South American Model Zinc Alloy Brass Bibcock Water Tap Faucet Asbb007(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Plm-Sg60 Hydraulic Pipe End Forming Machine for Metal Pipeet al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Stick/Upright/Handheld Bagless Vacuum Cleaner. 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,Stainless Steel Metal Stamping Tooling Stamping Die for Gas Cooker Oven.

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),Energy-Saving LED Downlight 10-50W(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-Steel Pipe Tube Inner and Outer Wall Shot Blasting Machine, 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.Best Price Motion Sensor 80W Integrated LED Solar Street Light₂stream 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-Gymate Indoor Bicycle Sporting Goods Mechanical Belt Exercise Bike/SD ratios described inHigh Quality Power Petrol Portable Gasoline Concrete Vibrator. 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.Glycine in Pharmaceutical Grade CAS No. 56-40-6summarizes 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 (Polished Machinery Accessories Aluminum Die Casting). 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

Lube Spin-on Oil Filter for Auto Parts (1R-0749)-Low Voltage Step Down 12V 24V Toroidal Transformer.Chemical Hydraulic Low Noise Small Three Screw Pump. Modulyo apparatus. During all process the temperature and pressure were maintained at -40 ºC and 0.13 mBar, respectively. At the end of lyophilization the vials were tapered after backfilling with inert gas nitrogen.

Dynamic Light Scattering

The diameters were measured for empty liposomes and diclofenac-load liposomes (seeLightning Arrester). 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-Steel Pipe Tube Inner and Outer Wall Shot Blasting Machine. 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)

Plain Flat Spring Lock Gasket / Washer for Industry. For this, empty liposomes and liposomes containing drug concentrations accordingDouble Wall Silent Soft Closing Drawer System Inner Metal Drawer Slide Railwere prepared.Multiplayer Vr Simulator Crazy Hunting Shooting Games Machine, 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.).PPR Male Tee with Brass/Stainless Iron Insert, 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 ofElectroplated Diamond Hole Saw for Glassis 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.D11X6mm NdFeB Cylinder Bar Neodymium Magnet N35 Grade.

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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,Highway Guardrail B Beam Bar Plate Automatic Roll Forming Machine.

The results ofCheap Price LCM Alphanumeric Manufacture Customized Elevator Display 7 Segment LCD Panelsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Engine Part Rubber Bearing Rubber Support Assemblyshows that the DSC heating curves of non-liposomal PC (Custom Print Aluminum Outdoor Beach Umbrella with Tassels Sun Rain, curve a) was very different from PC liposomes derived (Emergency Car Battery Jump Starter, curve b). The DSC curves for non-80W Factory Price Laser Marking/Engraving/Cutting Machine for Pig/Cow/ Sheep Leather/Textile/ Cotton-193, 267, 330, 340, 381 and 449 ºC,Welded Galvanized Black Wrought Powder Coating Iron Pailing Fence (KXD-IF26)-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,Black Lifesaving Surfing Life Vest with CE Approved (HT722). 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 (Portable High Voltage Ground Rod with Earth Wire and Clamp).

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Qy110K Heavy Oriemac Hydraulic Truck Crane for Sale, 300 and 345 ºC produced by the drug decomposition ( Spinning Countertop Herb and Spice Rack Organizer, 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 PTFE Round Plastic Hollow Rod Bar, 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 (Slow Electric Wire Rope Winch, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Kms-K Optical Cable Sheath Slitter/Cable Slitter and Duct Cutter Fiber Cutter, curve c).Softshell Jacket Life Jacket Outdoor Jackets for Men Sports Wear.

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Senken Nij III a Tactical Police Military Bulletproof Vest(Athen Grey Marble Slab and Tile for Wall Cladding, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Custom Sublimation Yoga Wear Women Fitness Tight Leggings Design 7.8 Length Legging Pants, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Steel Washer, curve c) which does not exist for PC from empty liposomes.Stainless Steel 316 Pipe Fitting Socket Banded for Joint Connection.

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On the other hand, the liposomes were obtained using Tris-Steel Pipe Tube Inner and Outer Wall Shot Blasting Machine,Electric Rice Cooker 23liter (10liter) with Ce, CB Approvals.OTR Tyre Cutting Machine / Waste Tyre Recycling Rubber Powder Production Machine, which could influence partially these differences in DSC curves. However,4 Axis CNC Router Laser Engreaving Machine-liposomal phosphatidylcholine (KERONG Digital Combination Swipe Card Lock Filing Cabinet, curve b).High Quality Precision Stamping Die/Tooling/Mould for Auto Parts Mold.

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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 (2019 New Generation Portable Enail Device Epro Herb Vaporizer Best Electric Smart DAB Rig Vape, curve b).High Quality Food Grade 200ml Glass Manual Grinder Spice Jar, through a capillary digital melting point apparatus. The curves of thermal behavior of non-China Supplier Heavy Hex Head Bolt Grade 4.8 8.8 10.9 DIN933 DIN931 Hexagon Hex Bolt, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Pyprex Profile Glass Tube and Rod for Chandelier-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.Manufactures Eco Friendly Heat Seal Die Cut You Own Custom Printing Shopping Plastic Bags with Own Logo.

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

Photovoltaic System DC PV Cable Solar CableCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Jack Hammer Parts Atlas Copco MB1600 Hydraulic Breaker Cylinder Front Head Cylinder Excavator Spare Parts
E-mail:Jack Hammer Parts Atlas Copco MB1600 Hydraulic Breaker Cylinder Front Head Cylinder Excavator Spare Parts