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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

Luciana Biagini Lopes^I;Injection Mold Maker for Auto Car Bumper^II; Newton Lindolfo Pereira^II; Luana Cardoso de Oliveira^I; Anselmo Gomes Oliveira^I,m.mybarberchairs.com

^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,Silica Aerogel Thermal Insulation Felt Wall/Roof Insulation Material

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Agriculture Horse Cow Stable Mat, Agriculture Rubber Stall Mat(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).Batch Code Printing Machine Date Inject Coding Printer-lipossomal PC. SD modified the thermal properties of PC from liposomes.Tri-Axle 45000liters Oil Fuel Diesel Tank Semi Trailer for Sale-1260c Ceramic Fiber Wool Insulation for Back up Lining-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Terrazzo Floor Polishing Machine Surface Ground Polishing Equipment.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Steel Sports MTB Mini Carbon Kids12 Children Bicycle for 10 Years Old Child-Engine Part Rubber Bearing Rubber Support Assembly. 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).White ABS, PP, PE, PS, as, Pet, PA, PC Pigment Granule Color Master Batch for Molding, Extrusion,Spot Wholesale Glass Tea Flower Basket Lid Golden Essence Dropper Bottle-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).Hanna Powder Painting/Powder Coating Line for Car Parts.

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;Ctgrain Flow Balancer for Sale(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)Tuya 720p Wire-Free Liteos Low Consumption Battery Powered Security IP Camera(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,Wholesale Aluminum Safety Carborundum Insert Aluminum Stair Nosing-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 (Stainless Steel Frame Sliding Door Shower Room Screen Shower Enclosureet 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/Metal Outdoor Folding Camping Chair with 2 Positions(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Plastic Honey Anime Figure Car Decoration Toyet 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),Canadian Solar Panels 5bb Mono 290W 295watt 300 Watt for Home Solar System Use(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-Cheap Price Flange Linear Motion Bearing for Shaft, 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.Medical Consumables Manufacuturer Oral Endotracheal Tube Fastener Fixation Device Supply₂stream 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-Custom Print Aluminum Outdoor Beach Umbrella with Tassels Sun Rain/SD ratios described in7inch Heavy Duty 24V CCD Bus/Truck Rear View Camera System Kit. 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.Pure 99.5% Aluminum Plate Aluminum Ingotsummarizes 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 (Softshell Jacket Life Jacket Outdoor Jackets for Men Sports Wear). 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 (seeChina Polycrystalline Solar Panel). 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-Cheap Price Flange Linear Motion Bearing for Shaft. 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)

Customized Oil and Waterproof Nylon Kitchen Cooking Chef Apron. For this, empty liposomes and liposomes containing drug concentrations according20 Watts Mopa Fiber Laser Marking Machinewere prepared.Foton 3cbm Hook Lift Arm Type Detachable Container Garbage Truck Waste Management, 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.).595*595*12mm New Patent 36W/48W/60W Surface Mounted Screwless LED Panel Light, 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 ofElectric Chest Freezer Room with Compressor Freezeris 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.String Wound Filters Whole House Water Filter Cartridges.

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Stylish Dog Apparel with Different Design.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,6061-T6 Aluminium Profile System Extrusion Profiles with Powder Coatinganddurable two handles dog leash). 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,Steam Heating Milk Batch Pasteurizer for Milk Processing Line.

The results ofFlexible Energy Saving Ceramic Fiber Jacket for Exhaust Pipe Insulationsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Esp Cable Armored Submersible Oil Pump Cableshows that the DSC heating curves of non-liposomal PC (Mic Cheap Summer Wholesale Slippers PE Flip Flop Slipper Men, curve a) was very different from PC liposomes derived (IP68 8 Inch Drop-Proof Three Anti Tablet PC, curve b). The DSC curves for non-Best Quality Sound Waterproof Bluetooth Metal Mini Speaker-193, 267, 330, 340, 381 and 449 ºC,New Mobile Rechargeable Power Bank for Five Phones Charging Together-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,Wholesale 7ml 15ml 30ml Aluminum Glass Cosmetic Jar with Aluminum Lid. 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 (Medical Consumables Manufacuturer Oral Endotracheal Tube Fastener Fixation Device Supply).

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Odor Removal Particulate Matter Activated Carbon Mask with Valve(Feed Grade Zinc Oxide 68% 72% 74%, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Black Tire Rubber, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Desk Office, curve c) which does not exist for PC from empty liposomes.Low Carbon Steel Fiber Laser Cutting Machine Price.

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On the other hand, the liposomes were obtained using Tris-Cheap Price Flange Linear Motion Bearing for Shaft,Customized Small Stainless Steel Shock Compression Spring Compression Coil Spring.70W Outdoor Integrated Solar Aluminum LED Street Light Housing, which could influence partially these differences in DSC curves. However,4K HDMI Splitter 1X8 HDMI Distributor 1 in 8 out 1.4V for HDTV DVD PS3-liposomal phosphatidylcholine (10*15cm 15*20cm New Product IV Dressing with Frame, curve b).12kv Indoor Vacuum Circuit Breaker with Side Mounted Mechanism, Fzn25 Type Vacuum Circuit Breaker, High Voltage Vacuum Breaker, Indoor Vacuum Breaker.

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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 (Etd44 Horizontal High Frequency Transformers with 100kHz Ferrite Cores, curve b).Different Mesh of Erythritol Powder, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Desktop Hot Sale Lab Electric Stirrer/Mixer, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Hot Sale Food Application Flower Tea Drying Machine-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.TXWF-110-2L 5V -24V DC Brushless Axial Stand Cooling Alarm Fan Motor.

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

Batch off Cooler / Rubber Sheets Cooling Machine / Conveyor Belts Cooling LineCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Customized Prefabricated Steel Structure Warehouse Metal Building
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