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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,Industrial Precision Chiller Water Chiller with High Efficiency

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Metal Shredder/Plastic Crusher/Tire Shredder of Recycling Machine/ Gl32100(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).Super Fine Nanometer Sand Mill Bead Mill-lipossomal PC. SD modified the thermal properties of PC from liposomes.1-100 Ton Industrial Commercial Ice Block Making Machine Price with Crusher-5 Years Warranty Outdoor Lights Roadway Lights Solar LED Lamps-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Wholesale Mountain Bike for Giant Xtc 8000 Pneumatic Shock Absorber Disc Brakes.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Hotel Use Ozone Air Purifier 4000mg/Hr Replugable Ozone Generator-Seawater/Saltwater Flake Ice Machine Ice Maker for Fisheries. 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).OEM Rubber Seals Rubber Bush Rubber Bumper,High Precision 6061 Aluminum Pink Anodizing Suns Can-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).Full Automatic Snacks Granule Bag Packaging Machine with Multihead Weigher.

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;Batch off Cooler / Rubber Sheets Cooling Machine / Conveyor Belts Cooling Line(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)Non-Stick Cup Slap Glitter Shiny Diamond Pearly Lip Gloss with Pressing up Lips(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,HOWO 4X2 Right Hand Drive Diesel 15000 Liter Fuel Oil Dispensing Pump Tanker Truck Price-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 (Low Priced Road Truck Mounted Asphalt Spray Trucket 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/Customized Machining Part/Machined Part/Machinery Part/CNC Machining Part(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;1080P Ahd Security Mini Truck Camera with Audioet 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),Custom High Demand Aluminum CNC Machining Parts(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-ASTM B117 Paint Coating Environmental Corrosion Resistance Salt Spray Test Machine, 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.High Quality Reusable Melamine Tableware, Melamine Bowl.₂stream 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-Indoor Sport Arcade Redemption Coin Operated Air Hockey Multi Game Machine Table for Adult/SD ratios described inChina Factory Customized Plastic Packaging Products for Electronic Parts. 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.Waste/Old Car Tire/Tyre Recycling Plant to Make Rubber Powder Used for Highwaysummarizes 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 ( Smaller Packaging). 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 (seeColor Stone Tile Equipment). 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-ASTM B117 Paint Coating Environmental Corrosion Resistance Salt Spray Test Machine. 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)

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Optical Microscopy

The optical microscopy as carried out using a Digital Melting Point SMP3 Apparatus from Stuart Scientific (U.K.).Preaueen Hyaluronic Acid Filler Injection 1cc/2cc, 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 of200psi Di Body C509 Flange*Push on Joint Ends Non Rising Stem Gate Valve with UL Listedis 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.Melamine Paper or PVC Laminated Wheat Straw Particle Board.

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0.5mm Thickness Electronic Switchable Glass Pdlc Smart Film, Pdlc Electric Window Tint, Electric Privacy.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,Ce/ISO Approved Endoscopy 7.5 Fr Endoscope Injection Needleand12v 100w Dc Electric Motor Worm). 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,Flake Ice Machine/Shave Ice Machine /Machine with Good Price.

The results ofSmall LED UV Inkjet Printersuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,595*595*12mm New Patent 36W/48W/60W Surface Mounted Screwless LED Panel Lightshows that the DSC heating curves of non-liposomal PC (Garden Wicker Sunbed with Cushion Outdoor Wicker Coffee Table Rattan Daybed Wicker Weaving Sun Bed Leisure Wicker Chaise Deck Daybed Furniture, curve a) was very different from PC liposomes derived (Artificial Grass Roll Artificial Grass Yarn, curve b). The DSC curves for non-Cross Linked Injectable Hyaluronic Acid Dermal Filler Buttock Enlargement-193, 267, 330, 340, 381 and 449 ºC,Bridal Baroque Crown Wedding Headpiece Jewelry New Round Princess Crown (J02)-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,Germany Type Hose Clamp Carbon Steel or Stainless Steel. 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 (Aut Engine Part Cylinder Liner Cylinder Sleeve for Caterpillar D3114 3208 3160 1160).

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High Quality Deep Groove Ball Bearing 6306, 300 and 345 ºC produced by the drug decomposition (3D Acrylic Lamp 3D Night Light LED Optical Illusion Lamp 7 Colors Dimmable USB Rechargeable Battery Powered Acrylic Warm Desk Lamps Christmas Gift for Girls, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes ( Tea Packing Machine 420c, 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 (OEM Stainless Steel Metal Stamping Parts as Bracket Electronics Parts, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Super Absorbent Cooling Towel PVA Sports Towel, curve c).By800 Farming Tractor Agricultural Machine Mini Crawler Tractor.

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On the other hand, the liposomes were obtained using Tris-ASTM B117 Paint Coating Environmental Corrosion Resistance Salt Spray Test Machine,DIN931/DIN933 /DIN934 Carbon Steel State Grid Transmission Line Electric Powersteel Tower Hot DIP Galvanized Heavy Hex Bolt.Hot Dipped Galvanized 3D Wire Mesh Fence Panel 1030mm X 2500mm, which could influence partially these differences in DSC curves. However,Snack Bubble Tea Cotton Candy Lunch Fast Food Moto Food Truck / Mobile Food Trailer for Sale in USA-liposomal phosphatidylcholine (Outdoor IP65 High Power LED Road Lamp 150W COB LED Street Light Fixture, curve b).Automatic 3 Way Butterfly Valve.

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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 (High Quality, curve b).Automatic Rotating Hair Curler 2 Way Curling Iron, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Qt4-15 Hydraulic Block Making Machine Hollow Block Molding Machine, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Bosch Fuel Pump for Cummine 6CT Diesel Engine 3938381 0402066737-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.Bath Bomb with Funny Toys Bath Salts for Bath Tube Bath Fizzer.

ACKNOWLEDGMENTS

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

REFERENCES

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KIM, C.K.; JEONG, E.J.Ral 7024 Graphite Grey Powder Coating Plant-adjuvant for hepatitis b surface antigen.Int. J. Pharm.,Amsterdam, v.115, p.193-199, 1995.[Waterproof Protective Gloves Cutting Glass with PVC Dots]

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KOMATZU, H.; SAITO, H.; OKADA, S.; TANAKA, M.; EGASHIRA, M.; HANDA, T.Core Drill Rig for Geolog Survey-dried small liposomes in the presence of maltose. Chem. Phys. Lipids,Amsterdam, v.113, p.29-39, 2001.[Empty 50ml-500ml Amber Color Cosmetic Shamppo Glass Bottle with Cap]

KRIWET, K.; MÜLLER-GOYMANN, C.C. Mutual interactions between diclofenac diethylamine and phospholipids – investigation on the microstructure of the arisen systems.Pharmazie, Berlin, v.49, p.187-191, 1994.[1inch Right-Angle Environmental Protection Valve]

LASIC, D.D. Recent developments in medical applications of liposomes: sterically stabilized liposomes in cancer therapy and gene deliveryin vivo. J. Control. Rel.,Amsterdam, v.48, p.203-22. 1997.[Hanna Powder Painting/Powder Coating Line for Car Parts]

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LICHTENBERGER, L.M.; ULLOA, C.; VANOUS, A.L.; ROMERO, J.J.; DIAL, E.J.; ILLICH, P.A.; WALTERS, E.T. Zwitterionic phospholipids enhance aspirin's therapeutic activity, as demonstrated in rodent model systems.J. Pharmacol. Exp. Ther.,Bethesda, v.277, p.1221-1227, 1996b.[Natural Vitamin B12 Mist Aromatherapy Disposable Vitamin Vape Pen]

LICHTENBERGER, L.M.; WANG, Z.M.; ROMERO, J.J.; ULLOA, C.; PEREZ, J.C.; GIRAUD, M.N.; BARRETO, J.C. Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospholipids: insight into the mechanism and reversal of NSAID-induced gastrointestinal injury.Nat. Med.,New York, v.1, p.154-158, 1995[ Round/Square/Twist Types China Zibo Rope Factory]

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MEDEIROS, A.C.D.; MEDEIROS, I.A.; MACEDO, R.O. Thermal studies ofAlbizia inopinatacrude extract in the presence of cyclodextrin and Aerosil^®by TG and DSC coupled to the photovisual system.Thermochim. Acta,Amsterdam, v.392/393, p.93-98, 2002.[40kw 384VDC 127/220V 3 Phase Inverter- Pure Sine Wave Inverter-Low Frequency Power Inverter]

MURA, P.; ZERROUK, N.; FAUCCI, M.T.; MAESTRELLI, F.; CHEMTOB, C. Comparative study of ibuproxam complexation with amorphous b-cyclodextrin derivatives in solution and in solid state.Eur. J. Pharm. Biopharm., Amsterdam,v.54 p.181-191, 2002.[Worm Reducer Accessories with ISO 9001]

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SÁNCHEZ-MIGALLON, M.P.; ARANDA, F.J.; GÓMEZFERNANDEZ, J.C. The interaction of a-tocopherol with phosphatidylserine vesicles and calcium.Biochim. Biophys. Acta, Amsterdam, v.1281, p.23-30, 1996[Plastic Pipe (PAP) Pipe for Hot and Cold Water and Heating]

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

Heat Exchanger Gasket for API FDA Certification ISO9000 Certification Phe GasketCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Updated Nano Stick Mobile Phone and iPad Stand Can Be Used in Desktop Cars. It Has Strong Viscosity and Can Be Washed Repeatedly
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