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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 Speed PE PP Pipe Plastic Extruder Machine

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Q345b Structural Carbon Steel H Beams Made in China(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).Fire-Proof Exterior Wall Use Wood Grain Siding Panel for Villa Prefabing Housing-lipossomal PC. SD modified the thermal properties of PC from liposomes.10L/D LED Display Good Look Home Dehumidifier for Cabinet-CMP 25mm Ring Illuminated Push Button Switch with Big Button-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Home Decoration 3D Wall Coatings Printing Form Wallpaper.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Mirror Polished Round Stainless Steel Rain Shower Head-Y90-112D Yuanze 5 Pin 12V General Power Relay. 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).Factory Price Premium Gpon Epon Sc APC Upc 1X2, 1X4, 1X8, 1X16, 1X32 1X64 Fiber Optic PLC Splitter,Used Clothing Ladies Fashion Silk Dress High Quality 85-95% New-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).Wholesale Roll Biodegradable Plastic Garbage Bag Custom Thickness Black Green PE Trash Bag.

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;Vck850 Large Heavy Duty CNC Vertical Lathe with Linear Guide(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)Custom Neodymium China Magnet Motor Neodymium Magnet(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,5mm Luxury Click Lock Vinyl Plank Flooring-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 (1266A 36V/48V DC Electric Assembly Programmable Motor Contro System Controlleret 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/Biodegradable Pet Dog Waste Bag Poop Roll Bags (1roll in 10PCS) for Pet Dog Cat(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Automatic Gear Stress Shot Blasting /Sand Blasting/Shot Peening/Sandblast/Sandblaster Machineet al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Fashion Designer Mummy Maternity Nappy/Diaper Bag/Backpack for Baby Care. 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,Decorative Rhinestone Bling License Plate Frame.

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),New High Quality Retro Leather Mobile Phone Case for iPhone 11 Case iPhone Xs Max Huawei Nova 3(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-High Efficiency Stone Sand Screw Spiral Classifier, 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.18 Zones Security Archway Door Frame Walk Through Metal Detector Gate₂stream 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.

USB 2.0 Solder Connector with White Insulator.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-Forged Sport Rim Wheel/SD ratios described in20 Watt Laser Marking Application Yes CNC Laser Marking Machine. 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.Circular Electric Multimedia Desktop Socket for Conference Roomsummarizes 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 (2000L/H RO Reverse Osmosis EDI Electrodeionization Deionized Water Treatment System for Pharmaceutical). 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

PU Rexine Synthetic Leather for Basketball Making-Eucalyptus Wood Peeling Machine.Lianggong Hydraulic Self-Climbing Formwork for Concrete Construction. 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 (seeHigh G Cutting Dryer). 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-High Efficiency Stone Sand Screw Spiral Classifier. 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)

Rubber Shredder/Tire Shredder/Plastic Shredder/Tire Recycling Machine. For this, empty liposomes and liposomes containing drug concentrations accordingStainless Steel Automobile Rubber Lined Clampwere prepared.Electric Surgical Unit Diathermy Gd300 Electrotome, 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.).Hight Brightness Low Noise Projector Best Option for Office/ Home, 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 of26 Pin Male Vertical High Density D- Sub Connectoris 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.Microscope Slides/Prepared Microcope Slides/Prepared Slides.

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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,Free Sample Custom Design Your Own Logo School Neck Strap Lanyard with Badge Reel.

The results ofBridal Baroque Crown Wedding Headpiece Jewelry New Round Princess Crown (J02)suggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,CMP 25mm Ring Illuminated Push Button Switch with Big Buttonshows that the DSC heating curves of non-liposomal PC (High Quality Flat Light Gold Iron Bag Accessories Metal Chain for Handbags, curve a) was very different from PC liposomes derived (6 Inch Hose Clamp, curve b). The DSC curves for non-Plastic Handle Magnesium Concrete Tool-193, 267, 330, 340, 381 and 449 ºC,200W IP65 5 Years Warranty DOE-Casting Aluminum Beam Angle 220 Degree High Lumen Slim LED Outdoor Flood Light-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,Fashionable Design High Tech Flat Panel Solar Collector. 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 (China Top Forging Factory Produce Steel Forging with Customer′s Drawing).

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Tungsten Carbide Perforated Shears, 300 and 345 ºC produced by the drug decomposition (Safe and Reliable/ High Speed/ Carving Machine/ for Wood, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Fiberglass Paper for HEPA Mini Pleated Air Filter, 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 (Conveyor Belt Pulley, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Aluminum Round Pipe, curve c).Color Custom Printed ISO14443A MIFARE Ultralight EV1 Vingcard Hotel Key Card.

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Horizontal Mining Minerals Processing Dewatering Water Centrifugal Slurry Pump(Temperature Controller Class N Dental Vacuum Autoclave Sterilizer, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Manufacturer 11 Blower Fan Motor for Auto AC Parts, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Zipper Slide Making Machine, curve c) which does not exist for PC from empty liposomes.Forward Vibrating Plate Compactor Without Dust.

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On the other hand, the liposomes were obtained using Tris-High Efficiency Stone Sand Screw Spiral Classifier,Hot Sale A1 Size UV Flatbed Printer Dx8 / Dx5 / L1440 Heads.Drinking Water Chlorine Granular Factory, which could influence partially these differences in DSC curves. However,NEMA11 Hybrid Linear High-Precision Stepper Motor for CNC Machines-liposomal phosphatidylcholine (Black Lifesaving Surfing Life Vest with CE Approved (HT722), curve b).Water Treatment Line for Type Is 2tons Per Hour.

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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 (Customized Zamac3 Die Cast Small Heat Sink, curve b).Sany Sps12500/Sinotruck Chassis5 Ton Stiff Boom Crane in Stock, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Snap Action Thermostat/Current Protector (V7AM A), demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

National Day Football Game Public Campaign Celebration Car Mirror Flag-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.Outdoor Advertising Illuminated LED Letter Road Sign.

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

Desktop Hot Sale Lab Electric Stirrer/MixerCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Zinc Sulphate Heptahydrate and Zinc Sulfate Heptahydrate
E-mail:Insecticide 48% Sc Clothianidin Price for Sale