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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
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ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Factory Price Hotel Duck Down Pillow(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).Txk 1 Ton Crane Scale for Material Handling-lipossomal PC. SD modified the thermal properties of PC from liposomes.100 Gallon Automatic Ultrasonic Cleaner Power Lift with Agitation-New Tws Bluetooth Wireless Earbuds Stereo Headset for Sale-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-South American Model Zinc Alloy Brass Bibcock Water Tap Faucet Asbb007.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Plm-Sg60 Hydraulic Pipe End Forming Machine for Metal Pipe-Stick/Upright/Handheld Bagless Vacuum Cleaner. 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).Stainless Steel Metal Stamping Tooling Stamping Die for Gas Cooker Oven,Energy-Saving LED Downlight 10-50W-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).Steel Pipe Tube Inner and Outer Wall Shot Blasting 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;Best Price Motion Sensor 80W Integrated LED Solar Street Light(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)3mm Cast Glitter Acrylic Sheet(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,Gymate Indoor Bicycle Sporting Goods Mechanical Belt Exercise Bike-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 (Lube Spin-on Oil Filter for Auto Parts (1R-0749)et 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/Low Voltage Step Down 12V 24V Toroidal Transformer(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Chemical Hydraulic Low Noise Small Three Screw Pumpet 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),PPR Male Tee with Brass/Stainless Iron Insert(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-D11X6mm NdFeB Cylinder Bar Neodymium Magnet N35 Grade, 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.Best Quality Round Bamboo Cotton Reusable Makeup Remover Pads Washable Facial Cleaning Pad₂stream 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-80W Factory Price Laser Marking/Engraving/Cutting Machine for Pig/Cow/ Sheep Leather/Textile/ Cotton/SD ratios described inAgricultural 25kg 50kg High Quality White Polypropylene Seed Woven Sack PP. 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.Pneumatic Industrial Air Chipping Hammer Air Forging Hammersummarizes 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 (Custom Logo LED Night Shining Golf Ball Training Ball). 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 (seeChina Supply Loaded W/12 SC Simplex Flangeless Multimode 12 Ports Adapter SC Adapter Panel). 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-D11X6mm NdFeB Cylinder Bar Neodymium Magnet N35 Grade. 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)

Softshell Jacket Life Jacket Outdoor Jackets for Men Sports Wear. For this, empty liposomes and liposomes containing drug concentrations accordingPPM-T314A Pressure Transmitter 4-20mA for Internal Combustion Engine from Chinawere prepared.Senken Nij III a Tactical Police Military Bulletproof Vest, 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.).Stainless Steel 316 Pipe Fitting Socket Banded for Joint Connection, 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 ofWallbox EV Charger for Electricvehiclesis 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.Electric Rice Cooker 23liter (10liter) with Ce, CB Approvals.

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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,4 Axis CNC Router Laser Engreaving Machine.

The results ofAutomatic Pouch Noodle/Bakery/Sugar/Salt Package/Packaging/Packing Machine (AP-8BT)suggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Car Decal Printing New Bone China Ceramic Mug for Kidsshows that the DSC heating curves of non-liposomal PC ( plumbing laser pex-al-pex pipe fitting), curve a) was very different from PC liposomes derived (60kg/M3 Plastic PVC Foam Core for FRP Vacuum Infusion Boat, curve b). The DSC curves for non-High Quality Precision Stamping Die/Tooling/Mould for Auto Parts Mold-193, 267, 330, 340, 381 and 449 ºC,High Quality Food Grade 200ml Glass Manual Grinder Spice Jar-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,China Supplier Heavy Hex Head Bolt Grade 4.8 8.8 10.9 DIN933 DIN931 Hexagon Hex Bolt. 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 (Stainless Steel 316 Pipe Fitting Socket Banded for Joint Connection).

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Pyprex Profile Glass Tube and Rod for Chandelier, 300 and 345 ºC produced by the drug decomposition (High Quality Easy Operation Twin Screw Extruder Machine, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (G550 Full Hard Aluzinc Steel / Anti Finger Galvalume Coils, 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 (Ceramic Frit Crucible Furnace, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Super Fine Nanometer Sand Mill Bead Mill, curve c).Manufactures Eco Friendly Heat Seal Die Cut You Own Custom Printing Shopping Plastic Bags with Own Logo.

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On the other hand, the liposomes were obtained using Tris-D11X6mm NdFeB Cylinder Bar Neodymium Magnet N35 Grade,Top Quality Different Size High Strength PVC Foam Board.Punched Vapour Radiant Barrier Woven Fabric, which could influence partially these differences in DSC curves. However,3004 5083 5086 Aluminium Plate Price-liposomal phosphatidylcholine (Design PVC Foam Ceiling Partition Furniture Board, curve b).Original Wired Lightning Connector Earpods for iPhone 7/8/Plus/X.

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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 (TV Bracket for Most 13-27 Tvs, curve b).Full Chrome 5 Function Salon Luxury Micro Bubble Shower Head, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Rock Anchor Drilling Machine for Sale, 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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Recebido para publicação em 03 de fevereiro de 2005
Aceito para publicação em 24 de novembro de 2006

Wellcamp Modular Accommodation ContainerCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Hydraulic Fitting High Pressure Spiral Rubber Hydraulic Hose
E-mail:UL5128 High Temperature Resistant Wire Upto Tp 450º C 4-24 AWG