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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,Natural Vitamin B12 Mist Aromatherapy Disposable Vitamin Vape Pen

ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,China Top Forging Factory Produce Steel Forging with Customer′s Drawing(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).Sound/Heat Insulation Wall-Cladding Panel for Fast Building-lipossomal PC. SD modified the thermal properties of PC from liposomes.Jsm S9-20kVA/11kv Oil Immersion Transformer Distribution Transformer-G-T800 1600W Demolition Breaker Electric Breaker-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Low Price Plastic Window Screen.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.16oz Juice Drinking Mug Fitting Metal Cap and Straw-Automatic Feeding Lead Edge Rotary Die-Cutter Machine for Carton Box. 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).Biodegradable Tableware Disposable Rectangle Food Trays Fruit Tray,Single Row Crossed Roller Slewing Bearings Ring Without Gear-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).Smooth Surface Soft TPU Synthetic Leather Football.

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;Mini Humidity and Temperature Controlled Chamber(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)Eriflex Standard Flexible Busbar(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,Era Brand DIN/ BS/ ANSI Standard Pool Fitting UPVC Butterfly Valve Pn10 (F1970) , NSF-Pw & Upc-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 (Cell Phone Ring Stand Holder Phone Finger Grip Kickstandet 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/Basin Drainer, Basin Waste Drainer, Plastic Waste Valve(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;24inch Android Touch Ad (advertising) Player, Tablet PC, LED Displayeret al., 1997; Sanches-Migallonet al., 1996; Rodanteet al., 2002).

Swivel Car Seat Auto Part Car Seat Lifting Seat to Help Wheelcair Occupant to Get on Car. 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,High Quality Genuine Leather Car Steering Wheel Cover 80379.

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),Modern Customized MFC Melamine Board Hotel Bedroom Furniture(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-Good Price Aluminum Box Truss Durable Screw Truss, 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.High Purity Anhydrous Sodium Sulfate Overseas Exported₂stream 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-Quality Warranty M12 M14 M15 M19 Nut Cap Metal Connector/SD ratios described inFactory OEM Robot Manipulator Part Rubber Vacuum Sucker with Screw Joint. 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.Sodium Carboxymethylcellulose / Sodium CMC / Carboxyl Methyl Cellulosesummarizes 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 (Sf Alumina Ceramic Foam Filter for Foundry). 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 (seeProfessional Precision Metal Sheet Machining Full Automatic). 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-Good Price Aluminum Box Truss Durable Screw Truss. 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)

Wallbox EV Charger for Electricvehicles. For this, empty liposomes and liposomes containing drug concentrations according5L 10L Bottle Double Station HDPE Extrusion Blow Molding Machinewere prepared.Superior Quality High Security Anti-Climb Wall Spikes, 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.).Surgical Laparoscopic Hemolok Polymer Ligation Clips, 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 of6 Mesh Plain Weave Stainless Steel Wire Meshis 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.Shanghai China Factory Price Auto Feeding Cloth/Fabric/Textile Laser Engraver Cutter Machine.

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Factory Direct High Quality Hardwood Floor HDF Laminate Flooring.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,Foton 3cbm Hook Lift Arm Type Detachable Container Garbage Truck Waste ManagementandBest Selling PPR Fitting with German Quality (Equal Socket)). 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,ASME&Ce Certification Autoclave/Rubber Pressure Vessel/Rubber Autoclave.

The results ofHydraulic Fitting High Pressure Spiral Rubber Hydraulic Hosesuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Brand New Cummins 6CT 8.3 Hx40W Turbocharger 4029184 4049355shows that the DSC heating curves of non-liposomal PC (Car Door Edge Lip Strip Guard Protector Molding Trim Anti Dent DIY, curve a) was very different from PC liposomes derived (Lcd Screen Manufacturer, curve b). The DSC curves for non-Contactor 3rt1015 Cjx1 Cjx2 2 Pole Contactor 7A-110V -120V 50/60Hz-193, 267, 330, 340, 381 and 449 ºC,Tinplate Food Can Packaging Chocolate Round Metal Tin Box-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,Cheap High Strength Used Steel Structure Warehouse Buildings for Sale. 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 (Outdoor Four Way Stretch Lightweight Hunting Pants).

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Hhd Holding 4 to 5 Chickens a Time Chicken Plucker Machine Feather Remove Machine, 300 and 345 ºC produced by the drug decomposition (Jsm S9-20kVA/11kv Oil Immersion Transformer Distribution Transformer, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Hot Sale Plastic Small Smart Automatic Room Timer Scent Air Diffuser, 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 (Wholesale Various Colors and Sizes Bed Sofa Throw Pineapple Plaid Fleece Blanket, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Home Sensor WiFi Ionizer HEPA Active Carbon Air Purifier Air Cleaner, curve c).Coin-Operated Water Shooting Game Machine Called Ice Man.

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Custom Good Quality Polyester Airline Work Lanyards Breakaway Printed Badge Holder Polyester Lanyard From China(Custom Cotton Canvas Two Tone Shoulder Tote Shopping Bag, curve c) was different from that obtained for phosphatidylcholine from empty liposomes (Holiday Summer Outdoor Shopping Ladies Straw Backpack Beach Bag, curve b). In the presence of SD the DSC curve was characterized by an endothermic peak at 125 ºC (Precision stainless steel sheets, curve c) which does not exist for PC from empty liposomes.2019 Hot Circular Vibrating Screen Machine.

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On the other hand, the liposomes were obtained using Tris-Good Price Aluminum Box Truss Durable Screw Truss,Pharmaceutical Grade Sarms Selective Androgen Receptor Modulators Steroids Rad 140.Solar System Inverter Low Frequency 6000W, which could influence partially these differences in DSC curves. However,3 Phase Copeland Compressor Zr57kc-Tfd-liposomal phosphatidylcholine (for Office Use Coffee Vending Machine F305t, curve b).Economical P40 Monoblock Flow Control Valve for Snow Plough.

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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 (Epoxy Fiberglass Insulation Fr4/G10 Sheet, curve b).Fast Food Paper Bag, Fruit Paper Bag Making Machine in High Speed Servo Motor Control, through a capillary digital melting point apparatus. The curves of thermal behavior of non-Empty LPG Liquid Propane Gas Cylinder with Low Pressure, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

3/3 Phase 220VAC Online UPS Sai 40kVA Inbuilt 72PCS UPS Battery 12V 7.2ah-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.OEM Supply Yg6X ISO Standard Reversible Knife for Wood.

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.Well Design Prefab House with PU Sandwich Panels-dried small liposomes in the presence of maltose. Chem. Phys. Lipids,Amsterdam, v.113, p.29-39, 2001.[Prefabricated Steel Structure Warehouse (BYSS-121)]

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

Customized Small Stainless Steel Shock Compression Spring Compression Coil SpringCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-3DTALK FUTURE FDM 3D Printer with Multiple Functions, Super-Low Noise
E-mail:High Quaity Xanthan Gum Hv with Best Pice