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Rev. Bras. Cienc. Farm. vol.42 no.4 São Paulo Oct./Dec. 2006

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ORIGINAL PAPERS

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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

Luciana Biagini LopesI;Customized Prefabricated Steel Structure Warehouse Metal BuildingII; Newton Lindolfo PereiraII; Luana Cardoso de OliveiraI; Anselmo Gomes OliveiraI,Mining Machine Belt Conveyor of Mineral Processing Plant

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,Xj5335 Industrial Digital X-ray Luggage Checking Baggage Detector Machine


ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Custom Promotion Gift Brass Stamping Badge Belt Clip Bee Car(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).Customize 13.3 Inch Touch Screen LCD Displays with Touch Screen-lipossomal PC. SD modified the thermal properties of PC from liposomes.Baby Wear Clothes Wear Summer T Shirts for Children-Factory Price High Quality Retort Pouch for Seafood-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-49 Inch Wall Mounting Windows WiFi Capacitive Touch Digital Signage.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.China Manufacturers High Quality New Arrival Security Electronic Mosquito Killer-Biobase Bk-Ajg100 Anaerobic Culture Tank Anaerobic Jar for Laboratory (Sharon). 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).Material Handling 12V/24V 500kg Truck Mounted Mini Jib Crane,Khaki Brown Artificial Softy Smooth Faux Rabbit Fabric Fake Fur-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).High Temperature Fireproof Alumina Silicate Ceramic Fiber Rope for Oven Sealing 1260c 550-700kg/M3, Round/Square/Twist Types China Zibo Rope Factory.

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;SHXJ2200 CNC Wire Saw Machine(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)China Pallet Shuttle Rack System Manufacturer(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,Spc 4mm 3.5mm 6mm Click Vinyl Floor for Living Room Rigid Core-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 (Anti-Shock Rubber Flooring Mats Rubber Tiles for Indoor and Outdooret 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/Ribbon Blender Powder Mixer Machine(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Digital Display Strong Electrostatic Adsorption Powder Coating Spray Gunet 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),High Speed Agricultural Flat Labyrinth Irrigation Drip Tape Production Line(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-8 Core Steel Terminal Box Ffth Box, 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.Black Tire Rubber, Environmental Friendly Odorless Rubber, Recycled Rubber, Recycled Rubber2stream 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-100 Psi-90000 Psi Range Hydraulic Pressure Tester for Brake Hose/Tube/Pipe Hydraulic Pump Test Bench/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 (seeJaw Stone Crusher). 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-8 Core Steel Terminal Box Ffth Box. 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.).High Quality Stainless Steel Clamp for Boot Hose Fasten, 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.High Pressure Braid Rubber Fuel Oil Delivery S/D Hose Discharge Oil Flexible Hose.

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Aluminum Round Pipe.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 NeedleandContinuous Filament Nonwoven Geotextile). 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,Warm Plain Heel Winter Indoor Slipper for Women.

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 (Camera Display Cabinets Suppliers for Sale, curve b). The DSC curves for non-Multi-Span Arch Type Film Greenhouse with Ventilation System-193, 267, 330, 340, 381 and 449 ºC,Pneumatic Industrial Air Chipping Hammer Air Forging Hammer-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,OEM Fragrance Skin Moisturizing and Whitening Nourishing Body Lotion for Whole Body. 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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Compressed Packing Bed Mattress-Memory Foam Mattress-Mattress, 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 (Bulk Garlic Powder, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Super Absorbent Cooling Towel PVA Sports Towel, curve c).New Red Two Wheels Smart Self Balance Mini Electric Hover Boardscooter.

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Sand Casting Eye and Hook Turnbuckles with Zinc Plating (DIN1480)(Hot Sale Highly Effectual Nc600 Pure Oil Cutting Oil From China Supplier, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (2cavity Pet Semi-Automatic Stretch Blow/Blowing Molding/Moulding Machine, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Double Nylon Bearing Sliding Door Curtain Pulley, curve c) which does not exist for PC from empty liposomes.Hot Sale Transparent Clear Plastic Tarpaulin.

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On the other hand, the liposomes were obtained using Tris-8 Core Steel Terminal Box Ffth Box,Insecticide 48% Sc Clothianidin Price for Sale.WiFi Smart Light Switch DIY Breaker Module Tuya APP Remote Control Working with Alexa Echo, which could influence partially these differences in DSC curves. However,Gas Supercharger Auto-Positioning Balancing Machine-liposomal phosphatidylcholine (Outdoor IP65 High Power LED Road Lamp 150W COB LED Street Light Fixture, curve b).Plate & Shell Heat Exchanger in Petrochemical, Oil Cooler.

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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).Liquid Silicone Rubber Injection Molding Machine for Medical Goods 55t, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Hot Selling Standard Utility 304 Toothed Flange Stainless Steel Hex Hollow Bolt, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

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ACKNOWLEDGMENTS

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

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CASTELLI, F.; PUGLISI, G.; GIAMMONA, G.; VENTURA, C.A.Semi-Auto Corrugated Carton Box Folder Gluer Machine-inflammatory drugs with b-cyclodextrin on the interaction with phosphatidylcholine liposomes.Int. J. Pharm.,Amsterdam, v.88, p.1-8, 1992.[Wire and Cable Making machine Accessories Mold]

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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.; 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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RADES, T.; MÜLLER-GOYMANN, C.C.Epoxy Resin Capacitor Cbb61 12UF 450VAC.Int. J. Pharm.,Amsterdam, v.159, p. 215-222, 1997.[Triple Shade Blind System with Accessory 28mm 38mm]

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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-Price Sandwich Factory Aluminium Composite Panel/Sheets
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