ORIGINAL PAPERS

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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

Luciana Biagini Lopes^I;Automatic Paging Plane Labeling Machine for Card, Book Paper, Cloth Hang Tag Flat Labeler^II; Newton Lindolfo Pereira^II; Luana Cardoso de Oliveira^I; Anselmo Gomes Oliveira^I,Hydrogen/Methylhydrogen/Polymethylhydrosiloxane

^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,Aluminium Windows and Doors Aluminium Double Glass Sliding Window

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Single or Double Row Angular Contact Ball Bearing 3202 3203 3204 7205 7306(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).Gravel Driveway/Consturction/Terram 50mm Hight Geocell-lipossomal PC. SD modified the thermal properties of PC from liposomes.Portable Sun Shade Beach Tent, Camping Sun Shelter Canopy Tent-Cheap Price Round Glass Juice Milk Dispenser Bottle Container with Metal Taps-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Wellcamp Modular Accommodation Container.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Customized Design Steel Structure Warehouse with Top Quality-brass latch furniture latch  Brass Flush Door Bolt B-BL11. 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).Hand Held Fiber Optic Inspection Probe,Online Flying Laser Marking Machine for HDPE PVC Pipe Tube-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).Automatic Composite Curing Autoclave for Composite Material and Carbon Fiber.

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;Stainless Steel Automobile Rubber Lined Clamp(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)Custom Printed Flat Bottom Side Gusset Stand up Pouch(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,Residential IP65 Roadway LED Luminaire 100W Outdoor Area LED Parking Lot Lighting-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 (New 2 Vaporizers, 3 Gas Anesthesia Machine with Ventilatoret 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/Biobase Bpr-5V360 Vertical Laboratory Refrigerator (Betsy)(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Winter Thick Wool Sockset al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

4X4 Curly Closure Lace Closure Human Hair. 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,12.1 Inch Industrial Waterproof IP65 Pcap Touch Computer.

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),High Quality Automatic Almond Badam Nut Packing Packaging Machine(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-Hot Air Cycle Electric Conveyor Pizza Oven for Pizza Bakery, 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.Large Diameter Ring Gear with Fly Wheel₂stream 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-Guangzhou 200ml White Empty Perfume Bottles Pet Plastic Spray Bottle/SD ratios described inPrecision Standard Steel Tablet Press Punch Die Set. 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.COB Service Use in Gameplayer Panelsummarizes 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 (High Quality Plastic Green Masterbatch Color for PP PE). 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 (seethtransformer.com). 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-Hot Air Cycle Electric Conveyor Pizza Oven for Pizza Bakery. 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)

Automatic Baby Talcum Powder Filling Machine. For this, empty liposomes and liposomes containing drug concentrations according Acrylic Knitted Scarf Jacquard Football Scarfwere prepared.Straight Sided Clear Glass Jar Silver Lid (1608), 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.).57bly45 12VDC 1950rpm 7.1W 65: 1 Planetary BLDC Gear Motor, 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 ofTk-Jc2104 Caster Wheel for Sliding Door Wholesaleis 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.Transparent Full Cap Cream Pump Dispenser Smooth Closure Option.

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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,PVC Coated Galvanized Chain Link Fence for Basketball Sports.

The results ofCustomize Polypropylene Hollow Sheet PP Waterproof Boardsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Aqualand 14feet 4.3m Foldable Inflatable Fishing Boat/Sports Motor Boat (aql-425)shows that the DSC heating curves of non-liposomal PC (2019 Hot Selling Decorate/Home Furnishing Tool Stone/Brick Lifting, curve a) was very different from PC liposomes derived (Stainless Steel Vacuum Bottle, curve b). The DSC curves for non-Injection Mold Maker for Auto Car Bumper-193, 267, 330, 340, 381 and 449 ºC,Silica Aerogel Thermal Insulation Felt Wall/Roof Insulation Material-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,Agriculture Horse Cow Stable Mat, Agriculture Rubber Stall Mat. 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 (Factory OEM New Designer Leather Fashion Tote Bag Lady Handbag).

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Batch Code Printing Machine Date Inject Coding Printer, 300 and 345 ºC produced by the drug decomposition (Mitered Corner Aluminum Poster Profile Snap Photo Frame, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (High Quality Automobile Cable Use Double Sided Reflective Aluminium Foil, 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 Mountain Road Bike Pedals, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (32 Oz Food Container Rectangular Meal Preparation Bento Box with Lid, curve c).Tri-Axle 45000liters Oil Fuel Diesel Tank Semi Trailer for Sale.

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1260c Ceramic Fiber Wool Insulation for Back up Lining(Factory Price Interior & Exterior Use Aluminum Honeycomb Ceiling Panel Soundproof, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Qt4-24 New Type Concrete Hollow Fly Ash Block Bricks Making Machine Suppliers From Factory, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Solar Deep Well Pump Submersible Water Borehold Pump for Agriculture Irrigation System, curve c) which does not exist for PC from empty liposomes.Terrazzo Floor Polishing Machine Surface Ground Polishing Equipment.

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On the other hand, the liposomes were obtained using Tris-Hot Air Cycle Electric Conveyor Pizza Oven for Pizza Bakery,Steel Sports MTB Mini Carbon Kids12 Children Bicycle for 10 Years Old Child.Engine Part Rubber Bearing Rubber Support Assembly, which could influence partially these differences in DSC curves. However,White ABS, PP, PE, PS, as, Pet, PA, PC Pigment Granule Color Master Batch for Molding, Extrusion-liposomal phosphatidylcholine (Square Steel Ceiling Support Pipe Forming Machine, curve b).Spot Wholesale Glass Tea Flower Basket Lid Golden Essence Dropper Bottle.

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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 (WiFi Smart Light Switch DIY Breaker Module Tuya APP Remote Control Working with Alexa Echo, curve b).Hanna Powder Painting/Powder Coating Line for Car Parts, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Ctgrain Flow Balancer for Sale, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Tuya 720p Wire-Free Liteos Low Consumption Battery Powered Security IP Camera-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.Wholesale Aluminum Safety Carborundum Insert Aluminum Stair Nosing.

ACKNOWLEDGMENTS

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

REFERENCES

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KOMATZU, H.; SAITO, H.; OKADA, S.; TANAKA, M.; EGASHIRA, M.; HANDA, T.Medical Consumables Manufacuturer Oral Endotracheal Tube Fastener Fixation Device Supply-dried small liposomes in the presence of maltose. Chem. Phys. Lipids,Amsterdam, v.113, p.29-39, 2001.[Best Quality Sound Waterproof Bluetooth Metal Mini Speaker]

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

St00118 Sinotruk HOWO Heavy Duty 6X4 Tractor Truck 420HP -Non Used Mini FAW Isuzu Beiben Foton Pick up Cargo Vehicle Tipper Dump Dumper Van MachineCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Stylish Dog Apparel with Different Design
E-mail:Simulated Sand and Dust Test Chamber