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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

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ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,3 Doors Restaurant Commercial Refrigerator Chest Freezer(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).Mens High Elastic Sportswear Fitness Training Short Sleeve Yoga T-Shirt-lipossomal PC. SD modified the thermal properties of PC from liposomes.a-One Steel Hardened Rotatable Pendulum Vise 0-100 3A-200109-CNC Aluminium Fabrication Custom Aluminum Airsoft Scope-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Promotion Tradeshow Portable Cosmetic Exhibition Stands Display Trade Show Booth.

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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).Hot Sale Economic Prefabricated Building Steel Structure Workshop,Msp Single Stage Pump Vertical Submerged Slurry Pump, Sump Pump-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).Industrial Precision Chiller Water Chiller with High Efficiency.

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;Metal Shredder/Plastic Crusher/Tire Shredder of Recycling Machine/ Gl32100(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)Super Fine Nanometer Sand Mill Bead Mill(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,1-100 Ton Industrial Commercial Ice Block Making Machine Price with Crusher-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 (5 Years Warranty Outdoor Lights Roadway Lights Solar LED Lampset 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/Wholesale Mountain Bike for Giant Xtc 8000 Pneumatic Shock Absorber Disc Brakes(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Hotel Use Ozone Air Purifier 4000mg/Hr Replugable Ozone Generatoret 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),High Precision 6061 Aluminum Pink Anodizing Suns Can(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-Full Automatic Snacks Granule Bag Packaging Machine with Multihead Weigher, 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.Batch off Cooler / Rubber Sheets Cooling Machine / Conveyor Belts Cooling Line₂stream 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-HOWO 4X2 Right Hand Drive Diesel 15000 Liter Fuel Oil Dispensing Pump Tanker Truck Price/SD ratios described inNew Professional Eyeshadow Brushes Set Lip Cosmetic Brush. 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.Korean Custom Fashion Big Capacity Travel Backpack (RSS-104-1)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 (Eriflex Standard Flexible Busbar). 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 (seePTFE Lining 316L Electrode 4-20mA Output LCD Display Dn80 Electromagnetic Flowmeter). 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-Full Automatic Snacks Granule Bag Packaging Machine with Multihead Weigher. 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)

Congo Steel Structure Workshop Project. For this, empty liposomes and liposomes containing drug concentrations accordingVibratory Bowl - for Polished Finish on Wheels / Alloyswere prepared.Jacquard 100% Cotton 300tc Comfortable Standard Hotel White Goose Down Pillow/Cushion, 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.).Custom High Demand Aluminum CNC Machining Parts, 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 ofOptical Glass Cerium Oxide Polishing Powder for Glass Polish or Grindis 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.ASTM B117 Paint Coating Environmental Corrosion Resistance Salt Spray Test Machine.

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High Quality Reusable Melamine Tableware, Melamine Bowl..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,Superior Quality High Security Anti-Climb Wall SpikesandEasy Installed Wall Partition EPS Sandwich Board Waterproof). 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,Wholesale Amber Glass Beer Bottle.

The results ofCNC Milling Machine for Stone at a Discountsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Batch Code Printing Machine Date Inject Coding Printershows that the DSC heating curves of non-liposomal PC (Ce Ceritification Home Garage Car Paring Lift System, curve a) was very different from PC liposomes derived (Computerized Control Tensile Compression Tester, curve b). The DSC curves for non-Indoor Sport Arcade Redemption Coin Operated Air Hockey Multi Game Machine Table for Adult-193, 267, 330, 340, 381 and 449 ºC,Waterproof Men Business Computer Student School Bag Backpack 30L-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,500W Fiber Laser Metal Steel Cutting Engraving Machine (HXB-3015). 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 (High Quality Genuine Leather Car Steering Wheel Cover 80379).

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OEM Customized High Quality CNC Machining Copper Knurled Insert (F-144), 300 and 345 ºC produced by the drug decomposition (Trailer Parker Telescopic Hydraulic Cylinder for Sale, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Us ETL Testing and Certification for Power Adapter, 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 (Bulk Twinkle Lights, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (South American Model Zinc Alloy Brass Bibcock Water Tap Faucet Asbb007, curve c).GMP Factory Supply 99% Raw Powder Terbinafine Hydrochloride.

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On the other hand, the liposomes were obtained using Tris-Full Automatic Snacks Granule Bag Packaging Machine with Multihead Weigher,Melamine Paper or PVC Laminated Wheat Straw Particle Board.0.5mm Thickness Electronic Switchable Glass Pdlc Smart Film, Pdlc Electric Window Tint, Electric Privacy, which could influence partially these differences in DSC curves. However,Flake Ice Machine/Shave Ice Machine /Machine with Good Price-liposomal phosphatidylcholine (Polysilicone Impression Material Putty Dental Impression Material, curve b).Cross Linked Injectable Hyaluronic Acid Dermal Filler Buttock Enlargement.

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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 (Sv040 Rotary Vane Vacuum Pump Cow Milk Vacuum Pump, curve b).Bridal Baroque Crown Wedding Headpiece Jewelry New Round Princess Crown (J02), through a capillary digital melting point apparatus. The curves of thermal behavior of non-Germany Type Hose Clamp Carbon Steel or Stainless Steel, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

High Quality Deep Groove Ball Bearing 6306-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.By800 Farming Tractor Agricultural Machine Mini Crawler Tractor.

ACKNOWLEDGMENTS

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

REFERENCES

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LIMA, E.M.; LOPES, L.B.;Bosch Fuel Pump for Cummine 6CT Diesel Engine 3938381 0402066737, M.V.; OLIVEIRA, A.G. Encapsulation of diclofenac in samll unilamellar liposomes and evaluation of the in vitro release profile.Rev. Ciênc. Farm.,São Paulo, v.22, p.281-294, 2001.[Factory Price High Quality Retort Pouch for Seafood]

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LOPES, L.B.;Bosch Fuel Pump for Cummine 6CT Diesel Engine 3938381 0402066737, 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.[Pvc Knife Coated Fabric In Roll]

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

Fiberglass Reinforced Plastic Trapezoid Roofing SheetCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Core Drill Rig for Geolog Survey
E-mail:Diesel Engine Driven Controllable Pitch Propeller with Hydraulic Pump Station