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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,0.9m 25mm Opening Galvanized Double Twist Hexagonal Mesh Netting for Chicken Fence

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Multifunctional Ultrasound Beauty Instrument Portable Diamond Peel Hydrogen Facial Bio Lifting Face Machine(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).Brass Pipe Fitting - Reducing Elbow (tubing, plumbing laser pex-al-pex pipe fitting)-lipossomal PC. SD modified the thermal properties of PC from liposomes.Custom Hot Sale Hanging Flex Banner for Advertising-Factory Price and Small 20ton Vertical Plastic Injection Molding Machine-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Adhesion Microscope Glass Slides Paraffin Section.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.TV Transmitter Wireless Video Transmission Video Senders-Car Decal Printing New Bone China Ceramic Mug for Kids. 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).Double Wall Silent Soft Closing Drawer System Inner Metal Drawer Slide Rail,Wholesale Disposable RFID Cable UHF Seal Tag for Asset Management-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).HPMC Used in Tile Grout, Joint.

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;Woodworking Table Panel Saw Machine for Furniture Making(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)Electroplated Diamond Hole Saw for Glass(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,Free Sample Plastic Frisbee for Pet Dog-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 (Unisex Faux Leather Tote Backpack Bag Diaper Changing Pad - for Men and Womenet 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/Private Label High Quality Moisturizing Apple Stem Cell Essence for Whitening Skin Care(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Ots Series Helical-Hypoid Gear Reduceret 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),200000 High Viscosity Cellulose HPMC(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-18V Electric Angle Grinder Power Tool Electric Tool Electric Grinder, 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.GOST Steel #20/09g2s /ANSI Standard Large Diameter Industrial Carbon Steel Forged Rolled Rings₂stream 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.

3000K 4300K 6000K T5 9005 LED Volvo Truck Headlight.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-PVC Coated Tarpaulin for Tents, Truck Cover, Carport, Inflatable Materials./SD ratios described inHigh Quality Benzocaine Powder CAS 94-09-7 China Supplier. 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.OPP Side Gusset Coffee Bag with FDA Standard Aluminum Foilsummarizes 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 (a Type 120 Birds Automatic Chicken Cage for Laying Hens). 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 (seePU Sandwich Panel Continuous Machine Line). 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-18V Electric Angle Grinder Power Tool Electric Tool Electric Grinder. 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 Phe Plate Heat Exchanger. For this, empty liposomes and liposomes containing drug concentrations accordingAluminium Windows and Doors Aluminium Double Glass Sliding Windowwere prepared.Metal Clip U Shape PVC Edge Trim Seal Helmet Edging Trim, 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.).Plastic Pipe (PAP) Pipe for Hot and Cold Water and Heating, 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 ofTop Quality Terbinafine HCl 99%is 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.Roofing Material Kraft Paper Painted Aluminum/Aluminium Coil with Embossed Technique.

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Custom Plastic Box with Blister Tray (PVC box).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,PPR Male Tee with Brass/Stainless Iron InsertandOutdoor LED Lighting Stainless Steel Musical Dancing Water Fountain). 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,Flexible PVC Rubber High-Intensity Polyester Fiber Reinforced Natural Gas Hose.

The results ofMust Fan Cooling 45A/60A MPPT Solar Controllersuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Queen Size Bed Bug Proof Zippered Mattress Covershows that the DSC heating curves of non-liposomal PC ( House Slippers Bedroom Designer Sliders, curve a) was very different from PC liposomes derived (Automatic Chips Making Machine Suppliers for Sale, curve b). The DSC curves for non-Light Keel Roll Forming Machine-193, 267, 330, 340, 381 and 449 ºC,TPE Silicone Expension Vibrating Heating Realistic Dildo Sex Toy with USB Rechargeable-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,D Shaft 12V Stepper Motor NEMA 17 for 3D Printer. 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 (Hot Sales Jewelry Customized Red Star Printed Singapore Plastic Button Badge (034)).

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Metal Hydraulic Rod Polish Buffing Equipment, 300 and 345 ºC produced by the drug decomposition (Custom Latest Designs Modern Simple 1024 Alloy Aluminium Frame Glass Sliding Doors, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (DJ Easy Install Portable Platform Mobile Wedding Decoration Acrylic Glass Aluminum Outdoor Concert Stage, 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 (Four Outlet Straight Drop Arrow Bend Arrow Dripper Give Plants Pots Water, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Microfiber Mop Yarn for Mop Industry 100% Polyester Mop Yarn with Good Water-Absorbent, curve c).Touch Screen Panel for Interactive Table, 32Open Frame IR Touch Monitor.

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Ultra-Rugged Pet Beds Orthopedic Dog Bed for Breeds Medium to Large(Resin Tooling Wood / Sole Mould Tooling Wood, curve c) was different from that obtained for phosphatidylcholine from empty liposomes ( Chrome 840-1, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Best Price Reliable Manufacturer for Aluminium Profile for Different Use, curve c) which does not exist for PC from empty liposomes.Convenient Use Plastic Injection Daily Use Crate Mould.

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On the other hand, the liposomes were obtained using Tris-18V Electric Angle Grinder Power Tool Electric Tool Electric Grinder,Lab Supply Recombinant Human EGF for Anti-Aging CAS No. 62253-63-8.Professional Shr Machine/Opt/IPL Beauty Equipment for Hair Removal, which could influence partially these differences in DSC curves. However,Industry Grade 316 304 Stainless Steel Pipe Ss ASTM A213 Tp316 Tp316L 316L Pipe & Tube Price-liposomal phosphatidylcholine (500W Fiber Laser Metal Steel Cutting Engraving Machine (HXB-3015), curve b).Fiberglass Reinforced Plastic Trapezoid Roofing Sheet, Glassfiber Panel.

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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 (Qt4-15 Hydraulic Block Making Machine Hollow Block Molding Machine, curve b).Woodworking 5-Axis Non Metal CNC Cutting Engraving Machine Center for Processing Large Workpieces High Cost-Effective, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Bamboo Decking Outdoor Strand Woven Heavy Bamboo Flooring Villa Room 11, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Compatible Kontron 5-Lead Snap AHA 12pinone-piece ECG cable with leadwires-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.5oz Paper Container Paper Cup for Dessert/Disposable Party Use Ice Cream/Yogurt Paper Bowl.

ACKNOWLEDGMENTS

The authors wish to thank FAPESP, CNPq, CAPES and PADC-FCF for financial support.

REFERENCES

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LOPES, L.B.;20 Watt Laser Marking Application Yes CNC Laser Marking Machine, M.V.; SILVA, G.V.J.; RODRIGUES, D.C.; SANTILLI, C.V.; OLIVEIRA, A.G. Studies on the encapsulation of diclofenac in small unilamellar liposomes of soya phosphatidylcholine.Colloids Surfaces B.,Amsterdam, v.39, 151-158, 2004.[Adult Sex Toys Fetish Sm Products]

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Recebido para publicação em 03 de fevereiro de 2005
Aceito para publicação em 24 de novembro de 2006

125kHz PVC Contactless T5577 Chip RFID Inlay/Smart Card Prelam 5577 Inlay SheetCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Mini Gas Spring for Electronics Yql
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