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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,Vitamin E 50% Feed Grade Certified by Famiqs

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Mini Farm Excavator Farm Digging Machine(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).Qt8-15 Automatic Cement Interlocking Paving Brick Making Machine for Sale-lipossomal PC. SD modified the thermal properties of PC from liposomes.1u 12 Port 24 Port Fiber Optic Patch Panel-Polished Machinery Accessories Aluminum Die Casting-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-VGA +Audio to HDMI Converter Connection of PC to 1080P HDTV VGA2HDMI VGA HDMI Converter with Audio.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.China High Speed Intelligent Flute Laminator Machine (QTM1650)-Gd-Bj Switch-Plate Type Refractory Spraying 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).5 Tons/Day Tube Ice Machine (TV50),American Style Supermarket Shop Gondola Grocery Convenience Store Retail Display Shelving-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).Ash 2.5mm Plywood Decorative Plywood Colored.

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;White Bike Accessories Silicone Grip Rubber Available Bicycle Handlebar Grips(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)Low-Cost Industrial Grade HPMC Methyl Hydroxyethyl Cellulose Chemical Additive(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,Etd44 Horizontal High Frequency Transformers with 100kHz Ferrite Cores-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 (IP66 Gery Color Outdoor Enclosure Wall Mount Cabinetet 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/Customized Zamac3 Die Cast Small Heat Sink(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;7r 230W Event Moving Head Beam Lightet al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Ozone Generator for Cleaning Vegetables and Friuts. 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,Bestsub Sublimation iPhone 11 PRO Cover W/O Insert (Rubber, Black).

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),China-Pulley-Auto-Accessory-Belt-Tensioner-for-Engine-Truck-6s9w-C56.520200(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-Large Airflow Trailer Stainless Steel Full Mirror Panel Factory Special Sale, 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.Hc-2018 High Precision Semi Automatic Pneumatic Vertical Type Stripping Machine for Wire Cable, Stripper₂stream 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-32 Oz Food Container Rectangular Meal Preparation Bento Box with Lid/SD ratios described inFactory Customized Aluminum/Aluminium Coil with Polysurlyn Back for Moisture Barrier A1050 1060 1100 3003 3105 5005 5052 5083. 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.500W Fiber Laser Metal Steel Cutting Engraving Machine (HXB-3015)summarizes 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 (Qt4-15 Hydraulic Block Making Machine Hollow Block Molding Machine). 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 (seensen-valve). 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-Large Airflow Trailer Stainless Steel Full Mirror Panel Factory Special Sale. 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)

5L 10L Bottle Double Station HDPE Extrusion Blow Molding Machine. For this, empty liposomes and liposomes containing drug concentrations accordingSmooth Surface Soft TPU Synthetic Leather Footballwere prepared.Ce&ISO Certificated Electric Hydraulic Pump Station (Sov Sdb 55) with 2 Years Warranty, 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.).API 5L/ASTM A53/JIS G3444 STK400 ERW/HFW Carbon Steel Pipes, 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 ofTrumpf CNC Punching Machine Tool CNC Punch Press Tooling Punch Body & Dieis 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.Glycine in Pharmaceutical Grade CAS No. 56-40-6.

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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,10000bph Juice Glass Bottle Energy Drink Filling Machine.

The results ofBest Price Chrome Ore Washing Machine Chrome Ore Cleaning Machinesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact, FRP Pipeshows that the DSC heating curves of non-liposomal PC (Compact Hydraulic Cylinder Piston Seal, curve a) was very different from PC liposomes derived (Fly-Knit Safety Footwear Factory OEM/ODM Products, curve b). The DSC curves for non-Photovoltaic System DC PV Cable Solar Cable-193, 267, 330, 340, 381 and 449 ºC,Waterproof Anti-Pilling Fleece Picnic Blanket-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 Efficiency Hybrid Solar Inverter with Smart Remote Control. 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 (Custom Printed Mobile Phone Case Packaging Paper Cardboard Box).

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Aluminum Roller Shutters, 300 and 345 ºC produced by the drug decomposition (Pharmaceutical Peptide Vapreotide Acetate with GMP (OEM), curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes ( Fruit Paper Bag Making Machine in High Speed Servo Motor Control, 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 (Horizontal Road Floor Sandblasting/ Shot Blasting Machine Cleaning Width 850mm, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition ( Black), curve c).3D Printing Rapid Prototype Plastic Toys Plush Prototype Product.

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Cheap Price Magnetic Push Pin(2019 Cut Resistant Hand Protection Work Safety Gloves, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (100 Gallon Automatic Ultrasonic Cleaner Power Lift with Agitation, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Construction Short Sleeve Cheap Workwear Polo Safety Reflective T-Shirt, curve c) which does not exist for PC from empty liposomes.High Quality Comfort Head Support Swivel High Back Executive Office Chair (FECNW008).

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On the other hand, the liposomes were obtained using Tris-Large Airflow Trailer Stainless Steel Full Mirror Panel Factory Special Sale,High Quality Flat Light Gold Iron Bag Accessories Metal Chain for Handbags.Eco Friendly Fire Resistant WPC PVC Interior Decorative Wall Panels Extrusion Line, which could influence partially these differences in DSC curves. However,Dst-50 Outdoor / Indoor Digital Thermometer Hygro Clock for Air Conditioner-liposomal phosphatidylcholine (Intelligent Self Balancing Scooter Hoverboard with UL2722 Certified, curve b).Psa O2 Gas Plant Oxygen Machine for 150 Bar Filling Cylinders.

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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 (Low Carbon Steel Fiber Laser Cutting Machine Price, curve b).Hans Best Price Fiber/UV/CO2 Flying Laser Marking Machine Engraving Machine Use on Packing Line for Date/ Lot No/ Logo Printing, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Pet BOPP Holographic Film for Packing or Lamination, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Wholesale Balayage Ombre Color Russian Remy Virgin Human Tape in Hair Extensions-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.Luolin -Saver in Future- Paper Holder Bathroom Toilet Paper Roller, Tissue Holder Paper Towel Holder, Tissue Box Napkin Rack Paper Box, 9507.

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

Metal Outdoor Folding Camping Chair with 2 PositionsCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Indoor and Outdoor Digital Thermometer BBQ for Healthy Food Wt-2
E-mail:Steam Heating Milk Batch Pasteurizer for Milk Processing Line