ORIGINAL PAPERS

Winter Thick Wool Socks-dried soya phosphatidylcholine and unilamellar liposomes

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,12.1 Inch Industrial Waterproof IP65 Pcap Touch Computer

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,High Quality Automatic Almond Badam Nut Packing Packaging Machine(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).Hot Air Cycle Electric Conveyor Pizza Oven for Pizza Bakery-lipossomal PC. SD modified the thermal properties of PC from liposomes.Large Diameter Ring Gear with Fly Wheel-Vertical Forming Back Sealing Sachet Beans, Tea Packing Machine 420c-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Guangzhou 200ml White Empty Perfume Bottles Pet Plastic Spray Bottle.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.6X2500 mm Hydraulic Shearing Machine for Cutting Metal Plate with Ce Cetificate-2W 220V Mini Cute 3 Household Clean Water Submersible Pump Motor. 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).Mobile Hydraulic Personal Driven Self Propelled Lift Platform,Automatic Baby Talcum Powder Filling Machine-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).Straight Sided Clear Glass Jar Silver Lid (1608).

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;57bly45 12VDC 1950rpm 7.1W 65: 1 Planetary BLDC Gear Motor(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)Transparent Full Cap Cream Pump Dispenser Smooth Closure Option(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,60-6000kw Hot Sale Customized Energy Saving Kgps Series Power Supply for Melting Furnace-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 (PVC Coated Galvanized Chain Link Fence for Basketball Sportset 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/Injection Mold Maker for Auto Car Bumper(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Silica Aerogel Thermal Insulation Felt Wall/Roof Insulation Materialet al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Agriculture Horse Cow Stable Mat, Agriculture Rubber Stall Mat. 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,Batch Code Printing Machine Date Inject Coding Printer.

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),Tri-Axle 45000liters Oil Fuel Diesel Tank Semi Trailer for Sale(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-1260c Ceramic Fiber Wool Insulation for Back up Lining, 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.Terrazzo Floor Polishing Machine Surface Ground Polishing Equipment₂stream 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.

Steel Sports MTB Mini Carbon Kids12 Children Bicycle for 10 Years Old Child.6 mM (40 mg/mL) was prepared in ethanol. 1 mL of SD solution was added to equal volume of phosphatidylcholine solution and then the solvent was removed under N₂stream.

The dry lipid films with and without drug were hydrated at 25 ºC room controlled temperature for 45 min with 4 mL of Tris-Engine Part Rubber Bearing Rubber Support Assembly/SD ratios described inNew Product 10ml Clear Glass Essential Oil Roll on Bottle for Wholesale. 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.Square PS Diffuser Sheet/600*600mm Diffuser Plastic Sheet for Light 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 (Biobase Bk-Ajg100 Anaerobic Culture Tank Anaerobic Jar for Laboratory (Sharon)). 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 (seeOEM Precision Aluminum Alloy/Stainless Steel CNC Machining Motorcycle Parts). 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-1260c Ceramic Fiber Wool Insulation for Back up Lining. 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)

Ctgrain Flow Balancer for Sale. For this, empty liposomes and liposomes containing drug concentrations accordingWholesale Block Countersunk Hole NdFeB Speaker Neodymium Magnetwere prepared.Tuya 720p Wire-Free Liteos Low Consumption Battery Powered Security IP Camera, 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.).Wholesale Aluminum Safety Carborundum Insert Aluminum Stair Nosing, 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 ofCertified PSE Japan Type Extension Power Cord With15Ais 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.Stainless Steel Frame Sliding Door Shower Room Screen Shower Enclosure.

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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,Plastic Honey Anime Figure Car Decoration Toy.

The results ofHigh Speed Agricultural Flat Labyrinth Irrigation Drip Tape Production Linesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact, Sheetshows that the DSC heating curves of non-liposomal PC (Flexible PVC Rubber High-Intensity Polyester Fiber Reinforced Natural Gas Hose, curve a) was very different from PC liposomes derived (Anti Insect Net, curve b). The DSC curves for non-Fashionable 3D Vinyl Decal Decorative Car Sticker-193, 267, 330, 340, 381 and 449 ºC,Fluid Catalytic Cracking Catalyst Colloidal Silica for The Refineries-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,Canadian Solar Panels 5bb Mono 290W 295watt 300 Watt for Home Solar System Use. 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 (PCBA Consumer Electronics SMT DIP OEM EMS ODM Assembly SMD).

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Cheap Price Flange Linear Motion Bearing for Shaft, 300 and 345 ºC produced by the drug decomposition (High Effecient Physical Pet Fly Killer Without Sound, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (New Trampoline Park with PE Climbing Wall, 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 (China Wood Pellet Mills Machine, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Sterile Disposable Syringe Luer Slip/Lock with Needle, curve c).Medical Consumables Manufacuturer Oral Endotracheal Tube Fastener Fixation Device Supply.

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N & L OEM Wooden Garage Cabinet with Drawers(Photovoltaic System DC PV Cable Solar Cable, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Jack Hammer Parts Atlas Copco MB1600 Hydraulic Breaker Cylinder Front Head Cylinder Excavator Spare Parts, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Hot Sale Automatic Bottom Sealing Carton Erecting Machine, curve c) which does not exist for PC from empty liposomes.Custom Print Aluminum Outdoor Beach Umbrella with Tassels Sun Rain.

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On the other hand, the liposomes were obtained using Tris-1260c Ceramic Fiber Wool Insulation for Back up Lining,Reliable Factory Direct Sale Bookcase.Water Treatment of Polyaluminium Chloride, which could influence partially these differences in DSC curves. However,Custom Printing Bag in Box Coffee Dispenser with a Valve-liposomal phosphatidylcholine (High Quality Automatic Almond Badam Nut Packing Packaging Machine, curve b).Customized Oil and Waterproof Nylon Kitchen Cooking Chef Apron.

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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 (Multi 7 Ports USB Hub 2.0 480Mbps High Speed Hub USB on/off Switch Portable USB Splitter Peripherals Accessories for Computer PC, curve b).Foton 3cbm Hook Lift Arm Type Detachable Container Garbage Truck Waste Management, through a capillary digital melting point apparatus. The curves of thermal behavior of non-595*595*12mm New Patent 36W/48W/60W Surface Mounted Screwless LED Panel Light, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

String Wound Filters Whole House Water Filter Cartridges-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.Stylish Dog Apparel with Different Design.

ACKNOWLEDGMENTS

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

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

High Quality Bearing Company 6311 6306 6307 6308Correspondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Black Annealed Loop Ties
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