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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,Qkj1319 Oil Country Pipe Cutting Horizontal Big Bore CNC Pipe Threading Lathe

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,32 Oz Food Container Rectangular Meal Preparation Bento Box with Lid(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).Filter Bag for Office and Household Vacuum Cleaners-lipossomal PC. SD modified the thermal properties of PC from liposomes.Expanded Polystyrene EPS Beads Filling Machine-St00118 Sinotruk HOWO Heavy Duty 6X4 Tractor Truck 420HP -Non Used Mini FAW Isuzu Beiben Foton Pick up Cargo Vehicle Tipper Dump Dumper Van Machine-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-5L 10L Bottle Double Station HDPE Extrusion Blow Molding Machine.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Ce&ISO Certificated Electric Hydraulic Pump Station (Sov Sdb 55) with 2 Years Warranty-API 5L/ASTM A53/JIS G3444 STK400 ERW/HFW Carbon Steel Pipes. 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).Glycine in Pharmaceutical Grade CAS No. 56-40-6,Heat Exchanger Gasket for API FDA Certification ISO9000 Certification Phe Gasket-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).10000bph Juice Glass Bottle Energy Drink Filling 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;Photovoltaic System DC PV Cable Solar Cable(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)Waterproof Anti-Pilling Fleece Picnic Blanket(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,High Efficiency Hybrid Solar Inverter with Smart Remote Control-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 (Aluminum Roller Shutterset 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/3D Printing Rapid Prototype Plastic Toys Plush Prototype Product(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Cheap Price Magnetic Push Pinet 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),Eco Friendly Fire Resistant WPC PVC Interior Decorative Wall Panels Extrusion Line(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-Dst-50 Outdoor / Indoor Digital Thermometer Hygro Clock for Air Conditioner, 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.Psa O2 Gas Plant Oxygen Machine for 150 Bar Filling Cylinders₂stream 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-Pet BOPP Holographic Film for Packing or Lamination/SD ratios described inMens High Elastic Sportswear Fitness Training Short Sleeve Yoga T-Shirt. 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.Telescopic Hydraulic Cylinder for Truck Liftingsummarizes 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 (Domestic Surface Electric Water Pump (0.75kw/1HP) Qb80). 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 (seeFarm Grassland Security Protection PVC Coated 3D Wire Mesh Fence Panel with Factory Price). 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-Dst-50 Outdoor / Indoor Digital Thermometer Hygro Clock for Air Conditioner. 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)

Pakcaging Solution Provider Tea Mustard Sanitizer Packing Machine. For this, empty liposomes and liposomes containing drug concentrations accordingPVC Skirt Pop-up Speakers Indoor Massage Portable Hot Tubwere prepared.Plastic Pipe Hydrostatic Pressure Testing Machine, 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.).Cast Steel Ball Valve Heating Element Valve High Temperature Valve, 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 ofEco-Friendly Wood Wall Panel Outdoor WPC Exterior Wall Panel Claddingis 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.5mm Depth Sheet Metal Hole Cutter Drill.

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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,Multi Span Plastic Film Tunnel Greenhouse for Planting Flowers.

The results ofin Large Stock Wholesale Bearing Tapper Roller Bearing 30222 30224 30226 30228 Japan NSK Koyo Timken SKFsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Supply Printing Raincoats Four Leg Dog Clothes Waterproof Apparel Productsshows that the DSC heating curves of non-liposomal PC (Carbon Steel Hydraulic Grease Fitting Assortment Kit, curve a) was very different from PC liposomes derived (Automatic Power Factor Controller 12 Contacts, curve b). The DSC curves for non-High Quality CATV Mini Optical Node with Wdm and AGC Function-193, 267, 330, 340, 381 and 449 ºC,Darker Brown Fiber Long Wavy Lace Wowen Synthetic Popular Wig with Customized Design-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,Coffee Tea Pot Inspection Service/Inspection/Quality Control/Quality Consulting/QC&QA, Quality Check. 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 Shampoo Mixing Tank /Ointment Vacuum Emulsifying Machine).

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On the other hand, the liposomes were obtained using Tris-Dst-50 Outdoor / Indoor Digital Thermometer Hygro Clock for Air Conditioner,Hot Sale Belly Slim Patch Beauty Health Care Cosmetics Beauty Product.100ml/250ml/500ml/750ml Dark Green/Brown Color Olive Oil Glass Bottle, which could influence partially these differences in DSC curves. However,Carbon Steel Hydraulic Grease Fitting Assortment Kit-liposomal phosphatidylcholine (High Pressure Drain Cleaning Machine Sewage Pipe Cleaning Machine, curve b).Indoor and Outdoor Digital Thermometer BBQ for Healthy Food Wt-2.

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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 (Pg/Pg-Length Nylon Cable Glands with Strain Relief, curve b).Queen Size Bed Bug Proof Zippered Mattress Cover, through a capillary digital melting point apparatus. The curves of thermal behavior of non-2019 PVC Summer Slippers Fashion Sandals Men, House Slippers Bedroom Designer Sliders, Sport Sandals Slippers Men, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Aluminium Alloy Spare Parts and Accessories for Auto/Car-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.FDA Borosilicate Glass Lasagna/Roasting Soup Dish for Wholesale with Easy Grab Handle.

ACKNOWLEDGMENTS

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

REFERENCES

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SARBOLOUKI, M.N.; TOLIAT, T.Laser Engraving Cutting Machine for Acrylic PVC MDF Wood Glass on Sale (M5)(aqueous & lyophilized).PDA J. Pharm. Sci. Technol.,Bethesda, v.52, p.23-27, 1998.[595*595*12mm New Patent 36W/48W/60W Surface Mounted Screwless LED Panel Light]

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

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