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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,Waterproof Ss Body Mini LED 1W 3W Underground Recessed Concrete Lights

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Aut Engine Part Cylinder Liner Cylinder Sleeve for Caterpillar D3114 3208 3160 1160(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).Laser Engraving Cutting Machine for Acrylic PVC MDF Wood Glass on Sale (M5)-lipossomal PC. SD modified the thermal properties of PC from liposomes.CE Sh-4A Ceramic Magnetic Stirrer Lab Magnetic Stirrer-Diesel Engine Driven Controllable Pitch Propeller with Hydraulic Pump Station-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-100% Polyester Coral Fleece Pet Animal Blanket.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.0.9m 25mm Opening Galvanized Double Twist Hexagonal Mesh Netting for Chicken Fence-Multifunctional Ultrasound Beauty Instrument Portable Diamond Peel Hydrogen Facial Bio Lifting Face Machine. 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).Brass Pipe Fitting - Reducing Elbow (tubing, plumbing laser pex-al-pex pipe fitting),Custom Hot Sale Hanging Flex Banner for Advertising-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).Factory Price and Small 20ton Vertical Plastic Injection Molding Machine.

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;Adhesion Microscope Glass Slides Paraffin Section(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)TV Transmitter Wireless Video Transmission Video Senders(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,Car Decal Printing New Bone China Ceramic Mug for Kids-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 (Double Wall Silent Soft Closing Drawer System Inner Metal Drawer Slide Railet 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/Wholesale Disposable RFID Cable UHF Seal Tag for Asset Management(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;HPMC Used in Tile Grout, Jointet 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),Free Sample Plastic Frisbee for Pet Dog(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-Unisex Faux Leather Tote Backpack Bag Diaper Changing Pad - for Men and Women, 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.Private Label High Quality Moisturizing Apple Stem Cell Essence for Whitening Skin Care₂stream 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-Gas Powered Jack Hammer Rock Drilling for Drilling Rig/SD ratios described in1/2 Inch 79 Degree Sr K5.6 Fire Sprinkler. 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.Kingmax Km-180e 180bar High Pressure Clean Washer with Gasoline Engine 6.5HP Machine From Green Powersummarizes 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 (Slaughterhouse/Buther Waste Processing Machine for Meat and Bone Meal). 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

Asia Aluminum Group PVDF Powder Coated Curtain Wall Aluminum Frame-200000 High Viscosity Cellulose HPMC.18V Electric Angle Grinder Power Tool Electric Tool Electric Grinder. Modulyo apparatus. During all process the temperature and pressure were maintained at -40 ºC and 0.13 mBar, respectively. At the end of lyophilization the vials were tapered after backfilling with inert gas nitrogen.

Dynamic Light Scattering

The diameters were measured for empty liposomes and diclofenac-load liposomes (seeAir Grille Design). 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-Unisex Faux Leather Tote Backpack Bag Diaper Changing Pad - for Men and Women. 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)

GOST Steel #20/09g2s /ANSI Standard Large Diameter Industrial Carbon Steel Forged Rolled Rings. For this, empty liposomes and liposomes containing drug concentrations accordingSem816 Weichai Engine Bulldozer/Crawler Bulldozer/Bulldozerwere prepared.3000K 4300K 6000K T5 9005 LED Volvo Truck Headlight, 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.).PVC Coated Tarpaulin for Tents, Truck Cover, Carport, Inflatable Materials., 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 ofD2w Biodegradable Stand up Pouchis 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.New Arrival Gemstone Jewelry Rose Gold Color Turquoise Necklace Choker for Women.

Small

Descriptionmaterial: PP+ Cardboardsize: 280X315X50mmsuitable for: A4color: Black/Red/Green/Bluepackage Included: 1X Lever Arch File Folder.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,Outdoor Advertising Illuminated LED Letter Road SignandEpe Cotton Extrusion Line). 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,Environmental Protection Scc102b Long Effect Antirust Emulsified Oil From China Supplier.

The results ofESD Bubble Mailing Bag for PCB Packingsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Stainless Steel 304 Morning Glory Trumpet Water Jet Fountain Nozzleshows that the DSC heating curves of non-liposomal PC (Promotion Tradeshow Portable Cosmetic Exhibition Stands Display Trade Show Booth, curve a) was very different from PC liposomes derived (Beauty Facial Thread Lifting Polydioxanone with Needle Plla/Pdo/PDA Thread Lifting, curve b). The DSC curves for non-Sanitary Stainless Steel Phe Plate Heat Exchanger-193, 267, 330, 340, 381 and 449 ºC,Metal Clip U Shape PVC Edge Trim Seal Helmet Edging Trim-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,Plastic Pipe (PAP) Pipe for Hot and Cold Water and Heating. 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 (25W Solar Panel Bulb Power Lighting Kit Home DC System Generator+Remote Control).

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Roofing Material Kraft Paper Painted Aluminum/Aluminium Coil with Embossed Technique, 300 and 345 ºC produced by the drug decomposition (Expanded Polystyrene EPS Beads Filling Machine, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Corora Discharge Portable 20g/H Water Sterilization Ozone Generator with Mixing Pump, 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 (Cast Iron Body Ball Check Valves Flange Type, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (SMD Arrow Panel Rear View Mirror Turn Signal Indicator LED Side Light for Harley, curve c).Custom Plastic Box with Blister Tray (PVC box).

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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 (7W E27 B22 LED Corn Light with Good Quality, curve b).Ultra-Rugged Pet Beds Orthopedic Dog Bed for Breeds Medium to Large, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Convenient Use Plastic Injection Daily Use Crate Mould, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Lab Supply Recombinant Human EGF for Anti-Aging CAS No. 62253-63-8-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.Professional Shr Machine/Opt/IPL Beauty Equipment for Hair Removal.

ACKNOWLEDGMENTS

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

REFERENCES

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BRIGES, P.A.; TAYLOR, K.M.J.Fiberglass Reinforced Plastic Trapezoid Roofing Sheet, Glassfiber Panel-Woodworking 5-Axis Non Metal CNC Cutting Engraving Machine Center for Processing Large Workpieces High Cost-Effective.J. Pharm. Pharmacol., London,v.53, p.393-98, 2001.[Aluminum Wheel Polishing Machine Alloy Wheel Repair Lathe Machine for Sale Wrm28h]

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LOPES, L.B.;Hasco Plug Brass Mold Elbow Hydraulic Parts Hose Nipple Fitting, 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.[A3 Size 100 Sheets/Pack Light Heat Transfer Paper for T-Shirt Printing]

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

Feed Grade Zinc Oxide 68% 72% 74%Correspondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-TV Bracket for Most 13-27 Tvs
E-mail:Black Tire Rubber