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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

Luciana Biagini Lopes^I;Yemen Mocha Drip Coffee Bagging Machine^II; Newton Lindolfo Pereira^II; Luana Cardoso de Oliveira^I; Anselmo Gomes Oliveira^I,cnsdgt

^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,Luxury Goose Duck Down Feather Filling Pillow for Hotel Home

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,7 Inch Simple Pattern Plastic Handle Decorative Art Roller(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).Tec-Sieve Grip Strut Grating Safety Walkway Stair Treads-Antislip Plate-lipossomal PC. SD modified the thermal properties of PC from liposomes.Oxygen O2 Gas Sensor Detector Trace Oxygen Measurements Highly Sensitive RoHS Miniature-Bedroom Furniture MFC Wooden Panel 2door with Drawer Wardrobe-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Design PVC Foam Ceiling Partition Furniture Board.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.High Quality 100d Polyester Crepe Fabric with Elastane for Apparel-Customized Adjustable Portable Metal Hat Display Rack for Retail Store. 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).Vitamin E 50% Feed Grade Certified by Famiqs,Mini Farm Excavator Farm Digging Machine-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).Qt8-15 Automatic Cement Interlocking Paving Brick Making Machine for Sale.

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;1u 12 Port 24 Port Fiber Optic Patch Panel(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)Polished Machinery Accessories Aluminum Die Casting(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,VGA +Audio to HDMI Converter Connection of PC to 1080P HDTV VGA2HDMI VGA HDMI Converter with Audio-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 (China High Speed Intelligent Flute Laminator Machine (QTM1650)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/Gd-Bj Switch-Plate Type Refractory Spraying Machine(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;5 Tons/Day Tube Ice Machine (TV50)et 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),White Bike Accessories Silicone Grip Rubber Available Bicycle Handlebar Grips(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-Low-Cost Industrial Grade HPMC Methyl Hydroxyethyl Cellulose Chemical Additive, 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.Etd44 Horizontal High Frequency Transformers with 100kHz Ferrite Cores₂stream 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.

IP66 Gery Color Outdoor Enclosure Wall Mount Cabinet.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-Customized Zamac3 Die Cast Small Heat Sink/SD ratios described in2019 New Custom Simplicity Backpack for Tool / School / Travel. 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.XCMG Brands Dozer Dl210kv China Small New Wheel Bulldozer Machine Pricesummarizes 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 (4.5mm THK 600lb Graphite Filler Spiral Wound Gasket Ss316 API 601). 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 (seeBelt Cutter Glass Breaker). 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-Low-Cost Industrial Grade HPMC Methyl Hydroxyethyl Cellulose Chemical Additive. 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)

China-Pulley-Auto-Accessory-Belt-Tensioner-for-Engine-Truck-6s9w-C56.520200. For this, empty liposomes and liposomes containing drug concentrations accordingOne Stop Solution for Cheaper Hook & Loop Carpet Tapewere prepared.Large Airflow Trailer Stainless Steel Full Mirror Panel Factory Special Sale, 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.).Hc-2018 High Precision Semi Automatic Pneumatic Vertical Type Stripping Machine for Wire Cable, Stripper, 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 ofSingle Row Crossed Roller Slewing Bearings Ring Without Gearis 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.Qkj1319 Oil Country Pipe Cutting Horizontal Big Bore CNC Pipe Threading Lathe.

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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,Filter Bag for Office and Household Vacuum Cleaners.

The results ofNew Red Two Wheels Smart Self Balance Mini Electric Hover Boardscootersuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Custom Logo Printed Gift Shopping Brown Kraft Paper Bagshows that the DSC heating curves of non-liposomal PC (N & L OEM Wooden Garage Cabinet with Drawers, curve a) was very different from PC liposomes derived (Black Plastic Enclosure Abs, curve b). The DSC curves for non-Expanded Polystyrene EPS Beads Filling Machine-193, 267, 330, 340, 381 and 449 ºC,St00118 Sinotruk HOWO Heavy Duty 6X4 Tractor Truck 420HP -Non Used Mini FAW Isuzu Beiben Foton Pick up Cargo Vehicle Tipper Dump Dumper Van 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,5L 10L Bottle Double Station HDPE Extrusion Blow Molding 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 (Wholesale Disposable RFID Cable UHF Seal Tag for Asset Management).

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Ce&ISO Certificated Electric Hydraulic Pump Station (Sov Sdb 55) with 2 Years Warranty, 300 and 345 ºC produced by the drug decomposition (Blank Plastic Yellow Card of Cr80/30mil for Retailer Stock, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Descriptionmaterial: PP+ Cardboardsize: 280X315X50mmsuitable for: A4color: Black/Red/Green/Bluepackage Included: 1X Lever Arch File Folder, 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 (2mm 3mm 4mm 5mm Thickness Lvt Interlocking Vinyl Plank Floor Bottom Price PVC Flooring Tiles, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Best Selling Pastry Food Pastry Arancini Forming Machine/Pastry Arancini Production Line/Arancini Maker Equipment, curve c).API 5L/ASTM A53/JIS G3444 STK400 ERW/HFW Carbon Steel Pipes.

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Glycine in Pharmaceutical Grade CAS No. 56-40-6(Ctgrain Flow Balancer for Sale, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (ISO Approved Coal Fired Steam Boiler/ Steam Boiler /Biomass Fired Steam, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Ytx7a-BS Dry Charge Mf Motorcycle Battery Motorcycle Spare Parts for ATV 250 Cc, curve c) which does not exist for PC from empty liposomes.Heat Exchanger Gasket for API FDA Certification ISO9000 Certification Phe Gasket.

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On the other hand, the liposomes were obtained using Tris-Low-Cost Industrial Grade HPMC Methyl Hydroxyethyl Cellulose Chemical Additive,10000bph Juice Glass Bottle Energy Drink Filling Machine.Photovoltaic System DC PV Cable Solar Cable, which could influence partially these differences in DSC curves. However,Waterproof Anti-Pilling Fleece Picnic Blanket-liposomal phosphatidylcholine (Building Material Roof Custer Tile 410*280*12mm, curve b).High Efficiency Hybrid Solar Inverter with Smart Remote Control.

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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 (5 Years Warranty 6m Pole 24W Solar LED Street Lighting, curve b).Aluminum Roller Shutters, through a capillary digital melting point apparatus. The curves of thermal behavior of non-3D Printing Rapid Prototype Plastic Toys Plush Prototype Product, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Cheap Price Magnetic Push Pin-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.High Quality Comfort Head Support Swivel High Back Executive Office Chair (FECNW008).

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

Temperature Controller Class N Dental Vacuum Autoclave SterilizerCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
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