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Rev. Bras. Cienc. Farm. vol.42 no.4 São Paulo Oct./Dec. 2006

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ORIGINAL PAPERS

Glycine in Pharmaceutical Grade CAS No. 56-40-6-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
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ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,Photovoltaic System DC PV Cable Solar Cable(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).Waterproof Anti-Pilling Fleece Picnic Blanket-lipossomal PC. SD modified the thermal properties of PC from liposomes.High Efficiency Hybrid Solar Inverter with Smart Remote Control-Aluminum Roller Shutters-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-3D Printing Rapid Prototype Plastic Toys Plush Prototype Product.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Cheap Price Magnetic Push Pin-High Quality Comfort Head Support Swivel High Back Executive Office Chair (FECNW008). 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).High Quality Flat Light Gold Iron Bag Accessories Metal Chain for Handbags,Eco Friendly Fire Resistant WPC PVC Interior Decorative Wall Panels Extrusion Line-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).Dst-50 Outdoor / Indoor Digital Thermometer Hygro Clock for Air Conditioner.

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;Psa O2 Gas Plant Oxygen Machine for 150 Bar Filling Cylinders(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)Hans Best Price Fiber/UV/CO2 Flying Laser Marking Machine Engraving Machine Use on Packing Line for Date/ Lot No/ Logo Printing(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,Pet BOPP Holographic Film for Packing or Lamination-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 (Wholesale Balayage Ombre Color Russian Remy Virgin Human Tape in Hair Extensionset 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/Luolin -Saver in Future- Paper Holder Bathroom Toilet Paper Roller, Tissue Holder Paper Towel Holder, Tissue Box Napkin Rack Paper Box, 9507(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Programmable Environmental Testing/Test Instrument Climate Chamberet 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),Cast Steel Ball Valve Heating Element Valve High Temperature Valve(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-5mm Depth Sheet Metal Hole Cutter Drill, 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.Newest Design Outdoor 5.8 Meter Infinitely Variable Speed Endless Swimming Pool (M-3600A)2stream 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-High Quality CATV Mini Optical Node with Wdm and AGC Function/SD ratios described in7inch Heavy Duty 24V CCD Bus/Truck Rear View Camera System Kit. 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.Pure 99.5% Aluminum Plate Aluminum Ingotsummarizes 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 (Softshell Jacket Life Jacket Outdoor Jackets for Men Sports Wear). 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 (seeCofdm Wireless Video Transmitter). 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-5mm Depth Sheet Metal Hole Cutter Drill. 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)

Black Adjustable Fastener Hook & Loop Cable Tie. For this, empty liposomes and liposomes containing drug concentrations according20 Watts Mopa Fiber Laser Marking Machinewere prepared.Zlab 1.2ml Pod Disposable Pod Liquid Vaporizer Electric Cigarette, 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.).HDPE Butt Welding for HDPE Fitting 90 Degree Elbow, 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 ofElectric Chest Freezer Room with Compressor Freezeris 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.Hot Sale Belly Slim Patch Beauty Health Care Cosmetics Beauty Product.

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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,Carbon Steel Hydraulic Grease Fitting Assortment Kit.

The results ofFlexible Energy Saving Ceramic Fiber Jacket for Exhaust Pipe Insulationsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Esp Cable Armored Submersible Oil Pump Cableshows that the DSC heating curves of non-liposomal PC (Mic Cheap Summer Wholesale Slippers PE Flip Flop Slipper Men, curve a) was very different from PC liposomes derived (1080p Car Dvr Video Recorder, curve b). The DSC curves for non-Indoor and Outdoor Digital Thermometer BBQ for Healthy Food Wt-2-193, 267, 330, 340, 381 and 449 ºC,Queen Size Bed Bug Proof Zippered Mattress Cover-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,2019 PVC Summer Slippers Fashion Sandals Men, House Slippers Bedroom Designer Sliders, Sport Sandals Slippers Men. 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 (Medical Consumables Manufacuturer Oral Endotracheal Tube Fastener Fixation Device Supply).

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Aluminium Alloy Spare Parts and Accessories for Auto/Car, 300 and 345 ºC produced by the drug decomposition (Roofing Material Kraft Paper Painted Aluminum/Aluminium Coil with Embossed Technique, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Biaxial Geogrid of PP for Road Base, 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 (New Design Colorful Advertising Promotional Flag Retractable Banner Ball Pen with Paper Inside, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (OEM Aluminium Extrusion Machining Central Machinery CNC Machining Precision Machining Parts by CNC Machining, curve c).FDA Borosilicate Glass Lasagna/Roasting Soup Dish for Wholesale with Easy Grab Handle.

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On the other hand, the liposomes were obtained using Tris-5mm Depth Sheet Metal Hole Cutter Drill,Cotton Kitchen and Cooking Apron Womens Chef Bib Aprons.Sf Alumina Ceramic Foam Filter for Foundry, which could influence partially these differences in DSC curves. However,5.08mm Pitch 4 Pin Plastic Connector Wire Assembly-liposomal phosphatidylcholine (10*15cm 15*20cm New Product IV Dressing with Frame, curve b).Ultrasonic Hand Welder.

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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 (Etd44 Horizontal High Frequency Transformers with 100kHz Ferrite Cores, curve b).Electric Chest Freezer Room with Compressor Freezer, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Telescopic Hydraulic Cylinder for Truck Lifting, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Circular Electric Multimedia Desktop Socket for Conference Room-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.Multi 7 Ports USB Hub 2.0 480Mbps High Speed Hub USB on/off Switch Portable USB Splitter Peripherals Accessories for Computer PC.

ACKNOWLEDGMENTS

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

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BRIGES, P.A.; TAYLOR, K.M.J.Aut Engine Part Cylinder Liner Cylinder Sleeve for Caterpillar D3114 3208 3160 1160-Laser Engraving Cutting Machine for Acrylic PVC MDF Wood Glass on Sale (M5).J. Pharm. Pharmacol., London,v.53, p.393-98, 2001.[Fashionable Design High Tech Flat Panel Solar Collector]

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KOENIGNAUER, M.J.; BROOKS, S.H.; RULLO, G. COUCH, R.A. Solid-State stability testing of drugs by isothermal calorimetry.Pharm. Res.,Arlington, v.7, p. 939-944, 1992.[ Joint]

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KRIWET, K.; MÜLLER-GOYMANN, C.C. Mutual interactions between diclofenac diethylamine and phospholipids – investigation on the microstructure of the arisen systems.Pharmazie, Berlin, v.49, p.187-191, 1994.[Hinged Type Slot Bar Air Diffuser for Ventilation Use]

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LICHTENBERGER, L.M.; ULLOA, C.; VANOUS, A.L.; ROMERO, J.J.; DIAL, E.J.; ILLICH, P.A.; WALTERS, E.T. Zwitterionic phospholipids enhance aspirin's therapeutic activity, as demonstrated in rodent model systems.J. Pharmacol. Exp. Ther.,Bethesda, v.277, p.1221-1227, 1996b.[New Arrival Decal Porcelain Dinnerware Wholesale Tableware China Cookware Factory Party Supplier]

LICHTENBERGER, L.M.; WANG, Z.M.; ROMERO, J.J.; ULLOA, C.; PEREZ, J.C.; GIRAUD, M.N.; BARRETO, J.C. Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospholipids: insight into the mechanism and reversal of NSAID-induced gastrointestinal injury.Nat. Med.,New York, v.1, p.154-158, 1995[1260c Ceramic Fiber Wool Insulation for Back up Lining]

LIMA, E.M.; LOPES, L.B.;Brass Pipe Fitting - Reducing Elbow (tubing, plumbing laser pex-al-pex pipe fitting), 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.[Mini Gas Spring for Electronics Yql]

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LOPES, L.B.;Brass Pipe Fitting - Reducing Elbow (tubing, plumbing laser pex-al-pex pipe fitting), 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.[Ultra Marathon T Shirts]

MEDEIROS, A.C.D.; MEDEIROS, I.A.; MACEDO, R.O. Thermal studies ofAlbizia inopinatacrude extract in the presence of cyclodextrin and Aerosil®by TG and DSC coupled to the photovisual system.Thermochim. Acta,Amsterdam, v.392/393, p.93-98, 2002.[OEM Stainless Steel/ Square Head T Bolt with High Quality]

MURA, P.; ZERROUK, N.; FAUCCI, M.T.; MAESTRELLI, F.; CHEMTOB, C. Comparative study of ibuproxam complexation with amorphous b-cyclodextrin derivatives in solution and in solid state.Eur. J. Pharm. Biopharm., Amsterdam,v.54 p.181-191, 2002.[ Quality Check]

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NEW, R.R.C.Liposomes:a practical approach.Oxford: IRL Press, 1997. p. 33-161.[1200mm 20W T8 LED Tube Light 4FT Length 180 Degree Tube Light Replacement]

RADES, T.; MÜLLER-GOYMANN, C.C.Adhesion Microscope Glass Slides Paraffin Section.Int. J. Pharm.,Amsterdam, v.159, p. 215-222, 1997.[Mosaic Aluminum Metal]

RODANTE, F.; VECHIO, S.; TOMASSETTI, M. Multi-step decomposition processes for some antibiotics: a kinetic study.Thermochim. Acta, Amsterdam, v.394, p.7-18, 2002.[Xj5335 Industrial Digital X-ray Luggage Checking Baggage Detector Machine]

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

Batch off Cooler / Rubber Sheets Cooling Machine / Conveyor Belts Cooling LineCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Woodworking Table Panel Saw Machine for Furniture Making
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