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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,High Quality Wood Debarking / Veneer Peeling Machine

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Coaxial Cable Rg59+Power Copper Cable OEM(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).Holiday Summer Outdoor Shopping Ladies Straw Backpack Beach Bag-lipossomal PC. SD modified the thermal properties of PC from liposomes.Dk7750AC EDM Cutting Molybdenum Wire EDM Wire Cut Machine-Black Wire Cloth (filter wire mesh)-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Outdoor IP65 High Power LED Road Lamp 150W COB LED Street Light Fixture.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.510 1ml Glass Vape Cartridge for Glass Vape Cbd Oil Vaporizer Vape Pen Cartridge-Ronggui Professional Nail Tools Foot Pedicure Callus Remover for Dead Skin Removal. 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).Leisure Type Office Seating with Leather Padding,PVC Sound Barrier Tarpaulin Factory Supply-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).Good Quality 50V Aluminum Electrolytic Capacitor.

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;Multilayer Automatic Extrusion Mould Machine with Ce(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)99% Liquid Solvent Materials Benzyl Benzoate to Treat Scabies(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,Automatic Pet Bottle Blowing Machine with Mold 7200bph-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 (1/4 Stainless Steel Meg Spray Nozzle for Pressure Washeret 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/0.14-2.5mm Thickness Hot Dipped Galvanized Steel Strip(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;9 Brushes Car Wash Tunnel Equipment Machine with Dryeret al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Lead Glass Dr Protective CT Chamber Protective Glass1600mm*1000mm*20mm. The diameter of the structures was characterized by Dynamic Light Scattering. The amorphous product derived from lyophilization was analyzed by DSC in order to verify the differences in the properties of PC,Brand New Cummins 6CT 8.3 Hx40W Turbocharger 4029184 4049355.

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),Foundation Blender Cosmetic Beauty Facial Makeup Sponge Puff for Cosmetics(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-High Quality Vodka Mini Wine Glass Shot Display Drinking Bar Club, 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 Power Petrol Portable Gasoline Concrete Vibrator₂stream 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.

High Quaity Xanthan Gum Hv with Best Pice.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 Large Big Drainage Pipe Tube Manufacturing Production Extrusion Machine/SD ratios described inChina Zibo Nature 5% 10% 18% Na2so4 Fdn-a Fdn-Ai Fdn-Aii Naphthalene Sulfonate Water-Reducing Admixture. 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.Stainless Steel Frame Sliding Door Shower Room Screen Shower Enclosuresummarizes 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 (450~1500mm Coil Width Stainless Steel Reversible Cold Rolling Mill). 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 (seeMost Popular 3 Function Affordable Nursing Bed Electric Hospital Bed). 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-High Quality Vodka Mini Wine Glass Shot Display Drinking Bar Club. 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)

High Quality Drum Heater, IBC Heater, Drum Heating Blanket, Heating Jacket for Drum, Tank, Cylinder. For this, empty liposomes and liposomes containing drug concentrations according3 Doors Restaurant Commercial Refrigerator Chest Freezerwere prepared.High Quality Automobile Cable Use Double Sided Reflective Aluminium Foil, 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 Pallet/Blow Pallet/HDPE Pallets/Storage Pallet/ Industry Pallet/Stackable Pallet, 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 ofChina Manufacturer Custom 3D Sublimation Digital Printing T Shirt Soccer Sports T-Shirtis 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.Different Sizes Seal Rubber Bellows for Automobile, Machinery Equipment.

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Dough Divider and Rounder Dough Divider and Dough Rounder.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,Fashion Jewelry Silver Jewelry Stainless Steel G23 Titanium Body Jewelry Red CZ Cuting Titanium Weddiing Ring Tr2029andm.maxwintool.com). 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,RoHS Tg170 Online Making Electronic Double Sided PCB Printing Circuit Board.

The results ofHigh Speed Automatic Alcohol Prep Pad Packaging Machinesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Vintage Furniture Metal Cafe Stainless Steel Dining Chairshows that the DSC heating curves of non-liposomal PC (Stainless Steel Cut Wire in Ripple or in Spools, curve a) was very different from PC liposomes derived (Cnc Suba Pipe Production Line, curve b). The DSC curves for non-Lifesrc Wholesales 1100 Gph 12V Boat Marine Plumbing-193, 267, 330, 340, 381 and 449 ºC,Sida Kbk-100 Industrial Dry Ice Block Making Machine Maker with New Vertical Dry Ice Block Generator-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,High Quality Bearing Company 6311 6306 6307 6308. 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 (High Purity Anhydrous Sodium Sulfate Overseas Exported).

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Customized CNC Machining Turning POM Plastic Aluminum Cleaning Equipment Parts, 300 and 345 ºC produced by the drug decomposition (High Temperature Resistant Precision Cylindrical Lithium Battery Machine Winder PU Silicon Rubber Japanese Standard Coating Roller, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (X-ray Machine System Medium & Small Vehicle Scanner, 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 (Direct Manufacturer Daf Machine Energy Saving Wastewater Treatment, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (High-Strength Factory Price Gi Galvanized Aluminium Corrugated Steel Roofing Sheet, curve c).Optimized Freight Wagon Exported to Ditterent Countries.

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Saudi ASTM A252 Grade 3 Carbon Steel Pipe ASTM A53(Sanitary Stainless Steel Phe Plate Heat Exchanger, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Jacquard 100% Cotton 300tc Comfortable Standard Hotel White Goose Down Pillow/Cushion, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Office furniture, curve c) which does not exist for PC from empty liposomes.Hot Sale Red Ring Necklace Earring Jewelry Box (6743R1).

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On the other hand, the liposomes were obtained using Tris-High Quality Vodka Mini Wine Glass Shot Display Drinking Bar Club,Wire and Cable Making machine Accessories Mold.Mc4 Solar Panel Connector 1000V for PV Cable 2.5/4/6mm Solar Panel Connect, which could influence partially these differences in DSC curves. However,Stainless Steel Cut Wire in Ripple or in Spools-liposomal phosphatidylcholine (Shanghai China Factory Price Auto Feeding Cloth/Fabric/Textile Laser Engraver Cutter Machine, curve b).50/2 Combed Ring Spun Cotton Yarn.

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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 (Unisex Faux Leather Tote Backpack Bag Diaper Changing Pad - for Men and Women, curve b).Cake Donut Packing Line/Automatic Commercial Donut Packaging Line, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Professional Factory Construction External Concrete Vibrator, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

PVC Laminated Calcium Silicate Ceiling Tile-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.10-40 PPI Zirconia Ceramic Foam Filter for Metal Filtration.

ACKNOWLEDGMENTS

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

REFERENCES

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High Quality, 23G, Blister Pack, Disposable Injection Needle for Medical, E.C.A.; ZHANG, W.; CROMMELIN, D.J.A.Think Vape Thor PRO Box Mod 220W-Intelligent Self Balancing Scooter Hoverboard with UL2722 Certified.Pharm. Res.,Arlington, v.9, p.1151-1160, 1997.[Welded Pipe ASTM]

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

Adm100sc Single Phase Energy Meter 5-30A KwhCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-High Strength 3 Strand Hawser Polyester /Polypropylene PP Mono Monofilament/ Nylon/ Marine Towing Rope for Mooring
E-mail:Customize Polypropylene Hollow Sheet PP Waterproof Board