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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,Factory Wholesale Customized Print Organza Ribbon with Satin Edge for Wrapping/Garments/Decoration/Wrapping/Christmas

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,China Manufacturer 3p 200A 250A 50Hz 380/410V 50ka Nsx250 MCCB(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).China Best Quality Exhaust Downpipe for Bwm F10 M5-lipossomal PC. SD modified the thermal properties of PC from liposomes.Fiberglass Mesh with High Quality and Low Price-Hot Sales Precision Casting Parts Dewaxing Casting Products-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-OEM Aluminium Extrusion Machining Central Machinery CNC Machining Precision Machining Parts by CNC Machining.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Plastic Stapler Office Stapler Book Stapler 213-Best Selling Cooking Press/Edible Oil Filter Refining Making 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).Higher Efficiency Cleaning Car Lawn High Pressure Water Washing Machine,Fiberglass Paper for HEPA Mini Pleated Air Filter-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).Manufacturer Custom Size Paper Bag with Logo.

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;Auto Horizontal Foam Cutting Machine (PQ)(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)Flower Printing PPGI / Special Pattern Coated Steel Sheet Coil / Pre-Painted Galvanized Steel Coil(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,Ce Restaurant Equipment Manual Sausage Filler Stainless Steel Filler-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 (Trumpf CNC Punching Machine Tool CNC Punch Press Tooling Punch Body & Dieet 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/Factory Direct Heavy Duty Garage/Office/Home Metal Drawer Tool Cabinet(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Round Rope Expanded PTFE for Industrial Valve-Spindle and Flange Sealset 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 Cheap Price M32 Explosion Proof Brass Metal Cable Gland(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-Supermarket Retail Advertising Accessories Transparent Plastic Shelf Dividers, 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.Mobile Phone Spare Parts Replacement LCD Screen for Redmi Note₂stream 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-Commercial Mini Glass Door Upright Showcase/SD ratios described inOts Series Helical-Hypoid Gear Reducer. 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.Smart Pdlc Film/Magic Dimming Intelligent Film for Glass Laminationsummarizes 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 (High Precision Customized Coal Mining Belt Conveyor Roller Idler). 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 (seeFolding Stillage). 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-Supermarket Retail Advertising Accessories Transparent Plastic Shelf Dividers. 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)

Luolin Shower System Pressure Balancing Valve Exposed Shower Set Rainfall Showerpipe, Chrome 840-1. For this, empty liposomes and liposomes containing drug concentrations accordingCustomized Machining Service CNC Hardware Milling Machining Componentswere prepared.7A Virgin Human Hair Brazilian Curly Virgin Hair with Closure, 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.).Rack Mount 19 Inch Cabinet, 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 of3/3 Phase 220VAC Online UPS Sai 40kVA Inbuilt 72PCS UPS Battery 12V 7.2ahis 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.Korean Custom Fashion Big Capacity Travel Backpack (RSS-104-1).

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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,2000L/H RO Reverse Osmosis EDI Electrodeionization Deionized Water Treatment System for Pharmaceutical.

The results ofRubber Hydraulic High Pressure Hosesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,China Factory Customized Plastic Packaging Products for Electronic Partsshows that the DSC heating curves of non-liposomal PC (Waste/Old Car Tire/Tyre Recycling Plant to Make Rubber Powder Used for Highway, curve a) was very different from PC liposomes derived (China Atc Ph Meter, curve b). The DSC curves for non-Food Grade High Quality Xanthan Gum Food Additives-193, 267, 330, 340, 381 and 449 ºC,Solar Power 10ka Mini Circuit Breaker 1pole 250V 1A 2A 3A 4A 6A 10A 16A 20A 25A 32A 40A 50A 63A DC MCB-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,Forged JIS Frame Rigging Eye and Eye Turnbuckle. 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 (Metal Sheet Stainless Steel Two Work Table with Machine Enclosed Cover Fiber Laser Cutting Machine).

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Sv040 Rotary Vane Vacuum Pump Cow Milk Vacuum Pump, 300 and 345 ºC produced by the drug decomposition (Custom Printed Flat Bottom Side Gusset Stand up Pouch, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (200psi Di Body C509 Flange*Push on Joint Ends Non Rising Stem Gate Valve with UL Listed, 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 (China 4ft Wood Core Veneer Peeling, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Mobile Phone Spare Parts Replacement LCD Screen for Redmi Note, curve c).Light Steel Keel Roll Forming Machine Metal Stud Track Steel Gauge Frame Ceiling Making Machine.

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On the other hand, the liposomes were obtained using Tris-Supermarket Retail Advertising Accessories Transparent Plastic Shelf Dividers,Kms-K Optical Cable Sheath Slitter/Cable Slitter and Duct Cutter Fiber Cutter.Stainless Steel 304 Morning Glory Trumpet Water Jet Fountain Nozzle, which could influence partially these differences in DSC curves. However,Custom Precision Machine Stainless Steel Aluminum Sheet Metal Welding Fabrication-liposomal phosphatidylcholine (Garden Wicker Sunbed with Cushion Outdoor Wicker Coffee Table Rattan Daybed Wicker Weaving Sun Bed Leisure Wicker Chaise Deck Daybed Furniture, curve b).Most Advanced Danish Motor Operated Portable Dental Chair Unit Dental Equipment.

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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 (Mc4 Solar Panel Connector 1000V for PV Cable 2.5/4/6mm Solar Panel Connect, curve b).Stainless Steel Vibrating Feeder for Conveyors, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Ce Cutting Plotters for Pattern Contour Cutting Plotter Cutter, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

5m Transparent Camping Geodesic Dome Tent for Display-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.New Model Smart Lighting Control Electric Touch Panel Wall Switch.

ACKNOWLEDGMENTS

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

REFERENCES

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

Full Chrome 5 Function Salon Luxury Micro Bubble Shower HeadCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Fiberglass Filtering Net for Foundry
E-mail:Plastic Pipe (PAP) Pipe for Hot and Cold Water and Heating