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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

Luciana Biagini Lopes^I;Rock Anchor Drilling Machine for Sale^II; Newton Lindolfo Pereira^II; Luana Cardoso de Oliveira^I; Anselmo Gomes Oliveira^I,Tr. PVC Sole Injection Machine

^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,Hard Cover Emboss A4 Faux Leather Book for Women

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Wood Furniture Room Electric Fireplace with Heater Fan Stove Remote Control(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).24128W33c3 24160k30W33c3 24122k30W33c3 24126W33c3 Industrial Machine Spherical Roller Bearing-lipossomal PC. SD modified the thermal properties of PC from liposomes.Stainless Steel Connecting Piece Machining Parts (HS-ST-014)-2019 New Design Big Capacity Comfortable Women′s 55L Hiking Backpack-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Must Fan Cooling 45A/60A MPPT Solar Controller.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Black PE Engineering Plastic Nylon Support Block-Brass Connector Copper Pipe and Tube Lugged Fitting. 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).0.50 Density PVC Forex Foam Board for outdoor Sign,Jack Hammer Parts Atlas Copco MB1600 Hydraulic Breaker Cylinder Front Head Cylinder Excavator Spare Parts-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).Biaxial Geogrid of PP for Road Base.

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;Hot Sale Popcorn Machine Used in Outdoor Food Kiosk/Mobile Food Carts/Street Food Cart Trailer 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)UL 94 Plastic Flammability Tester China Manufacture(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,Juice Bag Filling Machine Manufacturer for Small Business-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 (COB Service Use in Gameplayer Panelet 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/E-Shine Tc Material Grey and Silver Color 5cm Width High Visibility Reflective Fabric Tape Sew on Garment(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Flat Plate Pressure Solar Hot Water Heateret 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),Hydraulic Fitting High Pressure Spiral Rubber Hydraulic Hose(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-Stainless Steel + Glass 6-Jar Revolving Spice Storage / Jar Rack Organizer, Spinning Countertop Herb and Spice Rack Organizer, 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.Big Capacity Frozen Drinking Water Hand Carry Ss Sport Bottle₂stream 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.

25W Solar Panel Bulb Power Lighting Kit Home DC System Generator+Remote Control.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-7W E27 B22 LED Corn Light with Good Quality/SD ratios described inCosmetic Product Agitator Mixer Type Electric Heating Mixing Tank. 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.Sugar Nut Automatic Packing Machinesummarizes 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 (Customized Strong Colored PP Diamond Braided Rope for Bunding). 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 (seeChip For Bmw). 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-Stainless Steel + Glass 6-Jar Revolving Spice Storage / Jar Rack Organizer, Spinning Countertop Herb and Spice Rack Organizer. 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)

Universal Octopus Stand Tripod Mount Holder for Samsung iPhone Cell Phone. For this, empty liposomes and liposomes containing drug concentrations accordingHot Sale Brass / Zinc Shattaf Hand Held Bidet Sprayery2330)were prepared.Pharmaceutical Peptide Vapreotide Acetate with GMP (OEM), 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.).Aramid Fiber PTFE Packing, 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 of1000kgs Flake Ice Machine for Commercial Useis 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.Sectional Garage Door 2 Spring Bumper/Garage Door Bracket.

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Square Steel Ceiling Support Pipe Forming Machine.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,HOWO 4X2 Right Hand Drive Diesel 15000 Liter Fuel Oil Dispensing Pump Tanker Truck PriceandHot Customized Letter Printed Sport Gym Yoga Fitness Pants Leggings for Woman). 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,in Large Stock Wholesale Bearing Tapper Roller Bearing 30222 30224 30226 30228 Japan NSK Koyo Timken SKF.

The results of1 3-PCS Female Thread Screw PTFE Floating Stainless Steel Ball Valvesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Tunnel Electrical Spraying Shotcrete Machine with Spare Partsshows that the DSC heating curves of non-liposomal PC (CMC350L 3 Axis Vertical Universal CNC Cutting Milling Drilling Machine Tool Center, curve a) was very different from PC liposomes derived (www.qj-ec.com, curve b). The DSC curves for non-Gr2 Titanium Blind Pipe Floor Flange ANSI-193, 267, 330, 340, 381 and 449 ºC,Glass Bottle Wine Washing Filling Capping 3in1 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,1.78′′ Am OLED Display with 368*448 Resolution for Smart Watch. 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 (5oz Paper Container Paper Cup for Dessert/Disposable Party Use Ice Cream/Yogurt Paper Bowl).

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Marble Like 1.75mm 2.85mm PLA 3D Printing Filament, 300 and 345 ºC produced by the drug decomposition (Strength Exercise Equipment Abdominal Training Machine Commercial Gym Fitness Sports in Gym Room, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Electric Rice Cooker 23liter (10liter) with Ce, 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 (China Hand Held Shower Head, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Used Clothing Ladies Fashion Silk Dress High Quality 85-95% New, curve c).Natural Vitamin B12 Mist Aromatherapy Disposable Vitamin Vape Pen.

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On the other hand, the liposomes were obtained using Tris-Stainless Steel + Glass 6-Jar Revolving Spice Storage / Jar Rack Organizer, Spinning Countertop Herb and Spice Rack Organizer,Jsm S9-20kVA/11kv Oil Immersion Transformer Distribution Transformer.G-T800 1600W Demolition Breaker Electric Breaker, which could influence partially these differences in DSC curves. However,Low Price Plastic Window Screen-liposomal phosphatidylcholine (Sany 150 Ton Scc1500d Crawler Crane Hoisting Machinery, curve b).16oz Juice Drinking Mug Fitting Metal Cap and Straw.

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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 (Metal Round Storage Tin Storage Box Caddy, curve b).Automatic Feeding Lead Edge Rotary Die-Cutter Machine for Carton Box, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Biodegradable Tableware Disposable Rectangle Food Trays Fruit Tray, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Single Row Crossed Roller Slewing Bearings Ring Without Gear-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.Smooth Surface Soft TPU Synthetic Leather Football.

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

12 Rubber Edge Electroplated Injection Cone Speaker PartsCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Superior Quality High Security Anti-Climb Wall Spikes
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