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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,Wholesale Block Countersunk Hole NdFeB Speaker Neodymium Magnet

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,High-Strength Factory Price Gi Galvanized Aluminium Corrugated Steel Roofing Sheet(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).Pulley Apply to Metso Nordberg HP4 Cone Crusher Components-lipossomal PC. SD modified the thermal properties of PC from liposomes.40kw 384VDC 127/220V 3 Phase Inverter- Pure Sine Wave Inverter-Low Frequency Power Inverter-Digital Door Lock System, Intelligent RFID Card Hotel Lock-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Yojo AC250dq Brazed Plate Heat Exchanger Water HAVC Oil Food.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.American Truck Part Brake Chamber Original No.: T24/24dd-Cbb61 AC Motor Capacitor for Electric Fan Used. 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).Square Tea Tin Can/ Ttin Canister/Square Tin Jars,Black Smooth Finish ABS Plastic Injection Molded Items Speaker for Office Use-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).240V 4500W Industrial Immersion Tubular Heater Water Heater Heating Element.

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;Rsm-DCT (D) Core Hole Borehole TV Test(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)7inch Heavy Duty 24V CCD Bus/Truck Rear View Camera System Kit(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,FRP GRP Round Tube, Fiberglass Product Tube, FRP Pipe-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 (Customized High Quality Silicone PVC Airpods Protective Case for Earphoneet 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/Automatic Oil Bottle Filling Capping Sealing Machine with Factory Direct Supply(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Air Conditioning Fog System Water Humidifier Water Jet Clamp Nozzleet 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),65 4GB500GB I3 Floor Standing Touch All-in-One Kiosk Ad Player Advertising Display(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-Professional Elight IPL+RF Pigmentation Removal Hair Removal Beauty 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.Factory Wholesale Customized Print Organza Ribbon with Satin Edge for Wrapping/Garments/Decoration/Wrapping/Christmas₂stream 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-China Best Quality Exhaust Downpipe for Bwm F10 M5/SD ratios described in10-40 PPI Zirconia Ceramic Foam Filter for Metal Filtration. 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.104376-79-6 Ceftriaxone Sodiumsummarizes 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 (Pph Check Valve by DIN ANSI JIS). 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 (seeAlfagoma Hydraulic Hose). 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-Professional Elight IPL+RF Pigmentation Removal Hair Removal Beauty 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)

Plastic Stapler Office Stapler Book Stapler 213. For this, empty liposomes and liposomes containing drug concentrations accordingProfessional Elight IPL+RF Pigmentation Removal Hair Removal Beauty Machinewere prepared.Best Selling Cooking Press/Edible Oil Filter Refining Making 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.).Higher Efficiency Cleaning Car Lawn High Pressure Water Washing Machine, 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 ofCheap ABS Injection Molded Plastic Parts Molding Manufacturer for Saleis 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.Fiberglass Paper for HEPA Mini Pleated Air Filter.

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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,Auto Horizontal Foam Cutting Machine (PQ).

The results ofSwivel Car Seat Auto Part Car Seat Lifting Seat to Help Wheelcair Occupant to Get on Carsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Steel Pipe Tube Inner and Outer Wall Shot Blasting Machineshows that the DSC heating curves of non-liposomal PC (Automatic Sticker Bag/Hang Tag Paging Labeling Machine, curve a) was very different from PC liposomes derived (Newest White Duck Down and Feather with Best Price, curve b). The DSC curves for non-Flower Printing PPGI / Special Pattern Coated Steel Sheet Coil / Pre-Painted Galvanized Steel Coil-193, 267, 330, 340, 381 and 449 ºC,Ce Restaurant Equipment Manual Sausage Filler Stainless Steel Filler-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,Trumpf CNC Punching Machine Tool CNC Punch Press Tooling Punch Body & Die. 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 (7r 230W Event Moving Head Beam Light).

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Factory Direct Heavy Duty Garage/Office/Home Metal Drawer Tool Cabinet, 300 and 345 ºC produced by the drug decomposition (Injection Molded Soft Ribbed Rubber Silicone Handle Grip with Logo, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Mini Humidity and Temperature Controlled Chamber, 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 (Wooden Sliding Door Roller, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Professional Shr Machine/Opt/IPL Beauty Equipment for Hair Removal, curve c).Round Rope Expanded PTFE for Industrial Valve-Spindle and Flange Seals.

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On the other hand, the liposomes were obtained using Tris-Professional Elight IPL+RF Pigmentation Removal Hair Removal Beauty Machine,Free Sample Cheap Price M32 Explosion Proof Brass Metal Cable Gland.Supermarket Retail Advertising Accessories Transparent Plastic Shelf Dividers, which could influence partially these differences in DSC curves. However,Mobile Phone Spare Parts Replacement LCD Screen for Redmi Note-liposomal phosphatidylcholine (Rubber Shredder/Tire Shredder/Plastic Shredder/Tire Recycling Machine, curve b).Injection Molded Soft Ribbed Rubber Silicone Handle Grip with Logo.

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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 (Plate & Shell Heat Exchanger in Petrochemical, curve b).Commercial Mini Glass Door Upright Showcase, through a capillary digital melting point apparatus. The curves of thermal behavior of non-BSCI Factory Made Custom Metal Car Badge Personal Novel Decoration, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

CCTV 2MP HD P2p Digital Wireless WiFi Home Surveillance IP Network Camera System Kit-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 Supply Brand Fashion Light Safety Shoes.

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

Gi Steel GratingCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Stainless Steel Vibrating Feeder for Conveyors
E-mail:PVC Laminated Calcium Silicate Ceiling Tile