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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 Tolerance Blasting CNC Machining Service

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Wide Mouth Bottle Plastic Jar Blow Molding Machine Extrusion Blowing Moulding Machine 2 Cavities(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).Microfiber Cleaning Cloth for Glasses or Electronic Products-lipossomal PC. SD modified the thermal properties of PC from liposomes.Colorful Felt iPad/Laptop Bag Wholesale Felt Bags-High Steady 3D Foam Cutting CNC Router with 4 Axis/Foam Statue Making Machine/CNC Router Engraver-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Temperature Controller Class N Dental Vacuum Autoclave Sterilizer.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.OEM Hot Sale Basketball Soccer Rugby Pillow Cushion-Heavy Duty Metal Cupboard Cabinet/Furniture Hardware Door Stainless Steel Hinge. 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).12X24 Quick Installation Interlocking PVC Spc Vinyl Flooring Plank Tiles,Food Processing Stainless Steel Angle Seat Valve-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).PP Compression Fitting Cap Mold.

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;1000kgs Flake Ice Machine for Commercial Use(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)Xylitol FCCIV/USP, Smaller Packaging(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,Electro Galvanized Cattle Fence/ Filed Fence-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 (15cbm Sewage Sucking Tanker Vacuum Cleaner Suction Truck 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/Flower Pattern Color Printing PPGI Steel Coil Factory(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;SD16 D65 Ty165 Py165 Clg160 Dozer Transmission Shaft 16y-15-00061 16y-15-00061t 43A0108 63A0323et 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),Sany 150 Ton Scc1500d Crawler Crane Hoisting Machinery(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-C-Yark Public Address System Fire Power Amplifier, 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.Cr-V Professional Clamp Curved Jaw Locking Pliers Grip Pliers₂stream 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-Makute Electric Blower Mini Air Fan 600W Garden Tools/SD ratios described inAluminum Mylar Tape for Insulated Aluminum Ducts Made in China. 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.All-Ground Crane Grader Bridge Machine Double Act Small Piston Loader Dump Truck Lift Mobile Equipment Hydraulic Cylindersummarizes 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 (Laminate/Laminated Wooden Floor HDF MDF Best Factory in China). 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 (seeHotsale 500watt 600 1000W Watt Two 2 Wheel Folding Mini E-Scooter E-Bike Ebike). 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-C-Yark Public Address System Fire Power Amplifier. 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)

Sanitary Stainless Steel 304 316 Flange Adaptor. For this, empty liposomes and liposomes containing drug concentrations accordingDigital Display Strong Electrostatic Adsorption Powder Coating Spray Gunwere prepared.Ce & ISO China Dental Chair Equipment Dental Unit Chair, 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.).HOWO 6X4 Cargo Truck, 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 ofHand Held Fiber Optic Inspection Probeis 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.High Quality Plastic Green Masterbatch Color for PP PE.

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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,21 Years Experience Chinese Brand High Quality Horizontal Split Case Pump (TPOW).

The results of2017 EPA Approved Mini Go Karts/Dune Buggy/ATV with Ce for Kidssuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Waterproof Wood Plastic Composite Wall Panel WPC Cladding Machine Extrudershows that the DSC heating curves of non-liposomal PC (High Quality Mobile Phone LCD Touch Digitizer for iPhone 5/5g, curve a) was very different from PC liposomes derived (www.qiyymcft.com, curve b). The DSC curves for non-Bio Photon Light Therapy Machine Knee Pain Relief Health Care Supplement Beauty Equipment-193, 267, 330, 340, 381 and 449 ºC,Home Sensor WiFi Ionizer HEPA Active Carbon Air Purifier Air Cleaner-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,Alarm IR+UV Explosion Proof Flame Detector. 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 (Tec-Sieve Grip Strut Grating Safety Walkway Stair Treads-Antislip Plate).

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Tunnel Electrical Spraying Shotcrete Machine with Spare Parts, 300 and 345 ºC produced by the drug decomposition ( Drum Heating Blanket, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (High Efficiency Hybrid Solar Inverter with Smart Remote Control, 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 (MT01 ISO14443A Passive MIFARE Classic 1K Metal Mount RFID NFC Tag, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Custom Plastic Box with Blister Tray (PVC box), curve c).3 Axle Factory Outlet Car Carrier Semi Trailers for Sale.

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Epoxy Fiberglass Insulation Fr4/G10 Sheet(12 Rubber Edge Electroplated Injection Cone Speaker Parts, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Flexible Keyboard PCB Inverter Welding PCB Board PCB Components, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Solar Energy System with Solar Panel PV Mount Bracket, curve c) which does not exist for PC from empty liposomes.Mutrade Automatic Car Parking Systems/Hydraulic Lift.

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On the other hand, the liposomes were obtained using Tris-C-Yark Public Address System Fire Power Amplifier,Factory Aluminum Die Casting Auto Pump Parts.Industrial Air Flow Distribution Powder Curing Oven with Electrical Heater, which could influence partially these differences in DSC curves. However,Chicken Plucking Defeather Machine for Compact Poultry Farm Slaughtering Equipment-liposomal phosphatidylcholine (2019 Wholesale Multicolor Baby Sandal Leather Tassel Shoes, curve b).5000W Power Inverter DC 12V AC 220V for Lithium Battery.

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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 (Compatible Kontron 5-Lead Snap AHA 12pinone-piece ECG cable with leadwires, curve b).2019 Autumn and Winter Female Bat Sleeve Amazon Ins Fashion Sweater Jacket, through a capillary digital melting point apparatus. The curves of thermal behavior of non-China NSK NTN SKF Timken Deep Groove Ball Bearings, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

High Quality Mobile Phone LCD Touch Digitizer for iPhone 5/5g-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.Widely Used HVAC Pipe Leveling Beading Machine.

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

Gr2 Titanium Blind Pipe Floor Flange ANSICorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-High Brightness Outdoor Full Color LED Sign LED Display Board
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