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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,Customize Polypropylene Hollow Sheet PP Waterproof Board

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Polysilicone Impression Material Putty Dental Impression Material(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).Laminate/Laminated Wooden Floor HDF MDF Best Factory in China-lipossomal PC. SD modified the thermal properties of PC from liposomes.SPD Austrila Standard 45D Troughing Rollers and Frames-Feb018 3 Point Elr Seat Belt-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-High Rating 2 in 1 LCD Wave Hair Crimper Magic Curling Hair Styler Hair Curler Curling Iron.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.High Quality Drink Water Bottling Filling Machine Beverage Filling Equipment-Densen Customized Nodular Cast Iron Sand Casting and Machining Parts, Ductile Iron Fittings or Ductile Iron Flanges. 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).China Factory OEM Produce Custom Print Cotton Knit Terry Baby Bib Saliva Towel,Fast High Cut Bullet Proof Helmet with Night Vision Mount Kevlar/Aramid-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).Magnetic Level Meter with Flip Plate.

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;LCD Flying Color Fiber Laser Marking Machine for Metal Plastic PVC(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)CMC350L 3 Axis Vertical Universal CNC Cutting Milling Drilling Machine Tool Center(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,Hot Design LED Aluminum Profile-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 (1.8 * 2.5 M High Security 358 Anti -Climb Welded Fenceet 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/Fully Automatic Pillow Packing Machine(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Modern Home Furniture Living Room Chair Metal Leisure Chairet al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Computer Controlled Hydraulic Hose Crimping Machine (KM-91C-5). 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,JIS 201 / 202 / 304 / 304L 316 / 316L / 310S / 321 / 410 / 420 / 430 / 904L / 2205 / 2507 Stainless Steel Pipe Tube.

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),Soft Serve Ice Cream Making Machine For Sale(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-Multifunctional Hydro Oxygen Facial Aqua Water Peel Beauty Equipment SPA Use, 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.Hcvac Watchband PVD Mf Magnetron Sputtering Vacuum Coating Machine₂stream 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-50T Tube Ice Making/Maker Machine with Bitzer Compressor/SD ratios described inHard Cover Emboss A4 Faux Leather Book for Women. 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.10*15cm 15*20cm New Product IV Dressing with Framesummarizes 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 (Etd44 Horizontal High Frequency Transformers with 100kHz Ferrite Cores). 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 (seeMiddle East). 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-Multifunctional Hydro Oxygen Facial Aqua Water Peel Beauty Equipment SPA Use. 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)

Multilayer Board Flex PCB Circuit. For this, empty liposomes and liposomes containing drug concentrations accordingHot Sale High Quality Aluminum Speaker Boxwere prepared.5A/0.1A Current Transformer for Middle Frequency Induction Heater Components, 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.).Cjtouch 15 Capacitive Touch Screens Panel with USB Controller, 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 of30HP 2 Stroke Double Cylinders Boat Engine Propeller Engine Hood Outboard Engine 496cc Outboard Motor (T30BML)is 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.Activated Carbon Air Filter Ionic Purifier Air Purifiers Air Fresheners.

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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,Commercial Gym Fitness Sports Strength Exercise Equipment Abdominal Training Machine.

The results ofOEM Supply Yg6X ISO Standard Reversible Knife for Woodsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact, NSF-Pw & Upcshows that the DSC heating curves of non-liposomal PC (Black Adjustable Fastener Hook & Loop Cable Tie, curve a) was very different from PC liposomes derived (OEM Ductile Iron Pipe Fittings Joints Coupling, curve b). The DSC curves for non-Yellow Envelope Packaging Air Kraft Bubble Mailers Bag Custom Printed-193, 267, 330, 340, 381 and 449 ºC,Effective Weight Loss Capsules Slimming Pill, OEM Available-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,Smart Pdlc Film/Magic Dimming Intelligent Film for Glass Lamination. 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 (Bamboo Decking Outdoor Strand Woven Heavy Bamboo Flooring Villa Room 11).

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Women′s Seamless Fleece Lined Slim Jeggings Jean Leggings with Real Pockets, 300 and 345 ºC produced by the drug decomposition (E1 Grade Pine or Pillar or Falcata Melamine Block Board 1220X2440mm, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Hot Men′s Leather Hiking Shoes Trekking Shoes, 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 (Aluminum Die Casting Water Pump Body, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition ( Joint, curve c).Pph Check Valve by DIN ANSI JIS.

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GD 36T HDD machine for underground drilling/pipe laying(Hinged Type Slot Bar Air Diffuser for Ventilation Use, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Reliable Factory Direct Sale Bookcase, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Outdoor Textile Sunlounger Garden Sling Lounge Patio Furniture Garden Set Modern Furniture Outdoor Daybed, curve c) which does not exist for PC from empty liposomes.Air Fiberglass Roll Filter Media.

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On the other hand, the liposomes were obtained using Tris-Multifunctional Hydro Oxygen Facial Aqua Water Peel Beauty Equipment SPA Use,Wholesale Clear Transparent PMMA Plexiglass Plastic Sheet Acrylic Sheet.Portable High Voltage Ground Rod with Earth Wire and Clamp, which could influence partially these differences in DSC curves. However,Customized 3D Soft PVC Bottle Opener for Promotional Gift-liposomal phosphatidylcholine (1260c Ceramic Fiber Wool Insulation for Back up Lining, curve b).Empty 50ml-500ml Amber Color Cosmetic Shamppo Glass Bottle with Cap.

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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 (Cellulose Ether Mhec Used in Tile Cement From China Factory, curve b).Hair Dye Bowl Color Bowls Salon Bowl Hair Tint Dying Coloring Tool, through a capillary digital melting point apparatus. The curves of thermal behavior of non-2019 New Generation Portable Enail Device Epro Herb Vaporizer Best Electric Smart DAB Rig Vape, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

OPP Side Gusset Coffee Bag with FDA Standard Aluminum Foil-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.Hot Sales Jewelry Customized Red Star Printed Singapore Plastic Button Badge (034).

ACKNOWLEDGMENTS

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

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

Professional Manufacturer 3D Welded Wire Mesh FenceCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Aluminum Mylar Tape for Insulated Aluminum Ducts Made in China
E-mail:Air Cylinder/Compact Cylinder (SDA