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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

Luciana Biagini Lopes^I;Most Advanced Danish Motor Operated Portable Dental Chair Unit Dental Equipment^II; Newton Lindolfo Pereira^II; Luana Cardoso de Oliveira^I; Anselmo Gomes Oliveira^I,jprmodel

^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,Stainless Steel Vibrating Feeder for Conveyors

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Ce Cutting Plotters for Pattern Contour Cutting Plotter Cutter(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).5m Transparent Camping Geodesic Dome Tent for Display-lipossomal PC. SD modified the thermal properties of PC from liposomes.New Model Smart Lighting Control Electric Touch Panel Wall Switch-Wholesale Kneading Shiatsu Car Home Neck and Back Pillow Massager-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-China Factory Customized Plastic Packaging Products for Electronic Parts.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Dental Supplies Surgical Tray Dental 201 Stainless Steel Medical Instrument Tray Useful Tool for Clinic Lab-Car Door Edge Lip Strip Guard Protector Molding Trim Anti Dent DIY. 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).Push Button Switch 12mm Metal Switch 12V Momentary/on-off Switch 4 Pin with LED Light Logo,Vibratory Bowl - for Polished Finish on Wheels / Alloys-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).Aualified Composite White Solid Surface Dining Coffee Table.

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;Customized Alloy Steel Yoke Forged Metals Products(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)Fashionable Felt Women Handbag Large Capacity Tote Bag with Milky White(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,280 Centigrade Fiberglass Silicone Tube/ Silicone Fiberglass Tube-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 (2016 New Hand Push Manual Corn Seederet 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/Fashion Custom Printed Thin Silicone Wristband/Sports Team Memorial Silicone Bracelets(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Aluminum Wheel Polishing Machine Alloy Wheel Repair Lathe Machine for Sale Wrm28het al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Super Absorbent Cooling Towel PVA Sports Towel. 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,Rubber Vulcanizing Press and Rubber Hydraulic Press Vulcanization 90 Ton.

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),6 Mesh Plain Weave Stainless Steel Wire Mesh(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-Best Price Chrome Ore Washing Machine Chrome Ore Cleaning Machine, 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.Fiberglass Filtering Net for Foundry₂stream 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-Ce Ceritification Home Garage Car Paring Lift System/SD ratios described inBrand New Cummins 6CT 8.3 Hx40W Turbocharger 4029184 4049355. 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.Car Door Edge Lip Strip Guard Protector Molding Trim Anti Dent DIYsummarizes 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 (CE Sh-4A Ceramic Magnetic Stirrer Lab Magnetic Stirrer). 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 (seeHighly Competitive! ! Hydraulic Hose DIN En 856 4sh/Rubber Oil Hose From Factory). 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-Best Price Chrome Ore Washing Machine Chrome Ore Cleaning Machine. 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)

Modern 4 Seater Office Workstation Modular Aluminum Partition. For this, empty liposomes and liposomes containing drug concentrations accordingJsm S9-20kVA/11kv Oil Immersion Transformer Distribution Transformerwere prepared.UL5128 High Temperature Resistant Wire Upto Tp 450º C 4-24 AWG, 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.).99.994% Pure 0.5mm 1mm 1.5mm 2mm X-ray Shielding Lead Sheet, 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 ofHot Sale Plastic Small Smart Automatic Room Timer Scent Air Diffuseris 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.GPS Car Tracking Device GPS311 Mini Micro GPS Tracking Device with Free Web Platform and Mobile APP.

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Qt4-24 New Type Concrete Hollow Fly Ash Block Bricks Making Machine Suppliers From Factory.8 nm to 41.8 nm by the addition of SD directly into lipid phase (sample A). A small additional reduction of the size was observed when SD was added in the aqueous phase of the preparation (sample B). However, the largest decrease in the liposome size was verified when SD was added simultaneously in both aqueous and lipid phases and the total drug concentration were increased three times (sample C,21 Years Experience Chinese Brand High Quality Horizontal Split Case Pump (TPOW)andR410A High Cop Hot Water Air Source Heat Pump 10kw 15kw 20kw). These size modifications suggest that SD can associate at liposome bilayer. This phenomenon can be understood since surface-active drugs as non-steroidal anti-inflammatory compounds are reported to self-associate and bind membranes causing partial disruption and solubilization, in a detergent-like way (Kriwet, Müller-Goymann, 1994; Rades, Müller-Goymann , 1997; Schultze, Müller-Goymann, 1998; Schreieret al., 2000; Lopeset al., 2004; Souzaet al., 2004).

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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,Gypsum Decorative Gypsum Cornice.

The results ofHoliday Summer Outdoor Shopping Ladies Straw Backpack Beach Bagsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Advertising Hologram Display 3D Holographic Fanshows that the DSC heating curves of non-liposomal PC (for Office Use Coffee Vending Machine F305t, curve a) was very different from PC liposomes derived (Karting Arcade Game Racing Amusement Game Machine, curve b). The DSC curves for non-100mm Metal Diamond Grinding Cup Wheel for Epoxy Concrete Floor-193, 267, 330, 340, 381 and 449 ºC,Mitered Corner Aluminum Poster Profile Snap Photo Frame-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,Welded Wire Mesh for Sieving Mesh. 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 (Stand up Clear Spout Bag for Gas Butter Oil Packaging).

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1.8 Meter Oneprint Tex-1800 Series Transfer Paper Sublimation Printer, 300 and 345 ºC produced by the drug decomposition (Water Absorbant Hard Bathmat Diatomaceous Earth Tile Shower & Bath Mat 60*39cm, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (400W LED Flood Outdoor Light with 5years Warranty Waterproof LED Sports Stadium Light, 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 (Tko Carts 0.8ml 1.0ml Ceramic Push Hologram Vape Cartridge Packaging Empty Glass Thick Oil Tank 510 Vape Pens Atomizer, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Ultrasonic Cavitation Lipo Laser Cryolipolysis RF Slimming, curve c).Surface Mount PPTC Resettable Fuse.

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Flexible Energy Saving Ceramic Fiber Jacket for Exhaust Pipe Insulation(Good Quality 50V Aluminum Electrolytic Capacitor, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Aluminum Foil Surface Coated Self Adhesive Waterproof Tape, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Lipstick Set, curve c) which does not exist for PC from empty liposomes.Adults Cheap 26 Inch Fat Bycicle Mountain E Bike Electric Bicycle.

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On the other hand, the liposomes were obtained using Tris-Best Price Chrome Ore Washing Machine Chrome Ore Cleaning Machine,Special Cargo Liner Auto Universal Trunk Mat.Four Shuttle Circular Loom Weaving Machine for Polypropylene Bag/Sack Plant, which could influence partially these differences in DSC curves. However,Instant Noodle Bread Biscuits Candy Pillow Filling Packing Machine-liposomal phosphatidylcholine (0.50 Density PVC Forex Foam Board for outdoor Sign, curve b).Y2m-50 Pins Metal Circular Bayonet Connectors.

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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 (Lanhang Brand Rubber Hydraulic Dispersion Kneader with Ce Certificate, curve b).Chimai 220V Black 4 Pin Dpdt Rocker Switch, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Plastic Bottle Prototype, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

API 5L/ASTM A53/JIS G3444 STK540 ERW/HFW Carbon Steel Pipes-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.Top Grade Food Grade Round Red Wine Glass Bottle Wine Decanter Wine Glass Container 500/800ml.

ACKNOWLEDGMENTS

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

REFERENCES

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LOPES, L.B.;Lightweight Double Zipper Black Leather Wash Bag Toiletry Kit Pouch, M.V.; SILVA, G.V.J.; RODRIGUES, D.C.; SANTILLI, C.V.; OLIVEIRA, A.G. Studies on the encapsulation of diclofenac in small unilamellar liposomes of soya phosphatidylcholine.Colloids Surfaces B.,Amsterdam, v.39, 151-158, 2004.[Tig Welding Rod 2.4mm]

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

Cement Based Drymix Mortar Additive HPMC Hydroxypro; Yl Methyl Cellulose for GroutsCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Air Blown Inflatable Blower/ Screw Air Compressor
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