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vol.42 issue4Medication misadventures: how to minimize them?Development of formulations and technology of efavirenz coated tablets obtention: anti-HIV therapyauthor indexsubject indexarticles search
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Rev. Bras. Cienc. Farm. vol.42 no.4 São Paulo Oct./Dec. 2006

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ORIGINAL PAPERS

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Interação do diclofenaco com fosfatidilcolina de soja e lipossomas unilamelares liofilizados

Luciana Biagini LopesI;Stainless Steel Vibrating Feeder for ConveyorsII; Newton Lindolfo PereiraII; Luana Cardoso de OliveiraI; Anselmo Gomes OliveiraI,Lms For Small Business

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,Ce Cutting Plotters for Pattern Contour Cutting Plotter Cutter


ABSTRACT

Phospholipids are widely used as structural amphiphilic compounds in liposome formulations. In this study,5m Transparent Camping Geodesic Dome Tent for Display(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).New Model Smart Lighting Control Electric Touch Panel Wall Switch-lipossomal PC. SD modified the thermal properties of PC from liposomes.Wholesale Kneading Shiatsu Car Home Neck and Back Pillow Massager-China Factory Customized Plastic Packaging Products for Electronic Parts-260 ºC. The results of this work demonstrated that the presence of the drug modified the DSC behavior for both liposomal and non-Dental Supplies Surgical Tray Dental 201 Stainless Steel Medical Instrument Tray Useful Tool for Clinic Lab.

Uniterms:Liposome. Diclofenac. Phosphatidylcholine.Car Door Edge Lip Strip Guard Protector Molding Trim Anti Dent DIY-Push Button Switch 12mm Metal Switch 12V Momentary/on-off Switch 4 Pin with LED Light Logo. 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).Vibratory Bowl - for Polished Finish on Wheels / Alloys,Aualified Composite White Solid Surface Dining Coffee Table-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).Customized Alloy Steel Yoke Forged Metals Products.

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;Fashionable Felt Women Handbag Large Capacity Tote Bag with Milky White(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)280 Centigrade Fiberglass Silicone Tube/ Silicone Fiberglass Tube(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,2016 New Hand Push Manual Corn Seeder-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 (Fashion Custom Printed Thin Silicone Wristband/Sports Team Memorial Silicone Braceletset 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/Aluminum Wheel Polishing Machine Alloy Wheel Repair Lathe Machine for Sale Wrm28h(Bermúdezet al., 1999; Kinigt, 1981; Biltonen, Lichtenberg, 1993; Castelli,et al., 2001;Super Absorbent Cooling Towel PVA Sports Towelet 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),Best Price Chrome Ore Washing Machine Chrome Ore Cleaning Machine(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-Fiberglass Filtering Net for Foundry, 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.Fan Knit Scarves, Acrylic Scarf, Acrylic Knitted Scarf Jacquard Football Scarf2stream 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.

Ce Ceritification Home Garage Car Paring Lift System.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-Hot Sale PC LED Tube Light Housing Batten Extrusion Machine/SD ratios described inMirror Polished Round Stainless Steel Rain Shower Head. 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.Free Samples Customized Superior Quality BOPP Plastic Bag Food Packing Bag with Resealable Zipper for Dog/Cat Foodsummarizes 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 (Horizontal Heavy Duty Mill Discharge Centrifugal Slurry Pump). 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 (seeRhinestone Duckbill Clip). 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-Fiberglass Filtering Net for Foundry. 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)

UL5128 High Temperature Resistant Wire Upto Tp 450º C 4-24 AWG. For this, empty liposomes and liposomes containing drug concentrations according4 PCS Set Furniture Pads High Elastic Leg Shaper Sockswere prepared.99.994% Pure 0.5mm 1mm 1.5mm 2mm X-ray Shielding Lead Sheet, 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.).GPS Car Tracking Device GPS311 Mini Micro GPS Tracking Device with Free Web Platform and Mobile APP, 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 ofSupermarket Retail Advertising Accessories Transparent Plastic Shelf Dividersis 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.Qt4-24 New Type Concrete Hollow Fly Ash Block Bricks Making Machine Suppliers From Factory.

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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,100mm Metal Diamond Grinding Cup Wheel for Epoxy Concrete Floor.

The results ofHigh Quality Gantry CNC Plasma Cutting Machine for Metalsuggest that the DSC curve of PC can be dependent on the previous organization of PC molecules to form liposome bilayer. In fact,Aluminum Mylar Tape for Insulated Aluminum Ducts Made in Chinashows that the DSC heating curves of non-liposomal PC (All-Ground Crane Grader Bridge Machine Double Act Small Piston Loader Dump Truck Lift Mobile Equipment Hydraulic Cylinder, curve a) was very different from PC liposomes derived (Antislip Waterproof PVC Plastic Click Luxury Vinyl Flooring, curve b). The DSC curves for non-Mitered Corner Aluminum Poster Profile Snap Photo Frame-193, 267, 330, 340, 381 and 449 ºC,Welded Wire Mesh for Sieving Mesh-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,1.8 Meter Oneprint Tex-1800 Series Transfer Paper Sublimation Printer. 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 (5V 1.2A 6W DC USB Travel Mobile Phone Accessories).

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Surface Mount PPTC Resettable Fuse, 300 and 345 ºC produced by the drug decomposition (Digital Display Strong Electrostatic Adsorption Powder Coating Spray Gun, curve a) and is in agreement with the data of literature (Giordano,et al., 2003). The peaks at 141 ºC for empty liposomes (Hand Held Fiber Optic Inspection Probe, 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 (40cm Anti-Skid PVC Chemical Resistant Industrial Safety Work Gloves with Seamless Liner, curve c) and decreased significantly the peak intensity at 245 ºC due to product decomposition (Modern Home Furniture Living Room Chair Metal Leisure Chair, curve c).Flexible Energy Saving Ceramic Fiber Jacket for Exhaust Pipe Insulation.

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On the other hand, the liposomes were obtained using Tris-Fiberglass Filtering Net for Foundry,Four Shuttle Circular Loom Weaving Machine for Polypropylene Bag/Sack Plant.Instant Noodle Bread Biscuits Candy Pillow Filling Packing Machine, which could influence partially these differences in DSC curves. However,Y2m-50 Pins Metal Circular Bayonet Connectors-liposomal phosphatidylcholine (High Quality Mobile Phone LCD Touch Digitizer for iPhone 5/5g, curve b).Chimai 220V Black 4 Pin Dpdt Rocker Switch.

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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 (Woodworking Table Panel Saw Machine for Furniture Making, curve b).Plastic Bottle Prototype, through a capillary digital melting point apparatus. The curves of thermal behavior of non-API 5L/ASTM A53/JIS G3444 STK540 ERW/HFW Carbon Steel Pipes, demonstrating that SD molecules interact with phosphatidylcholine even in the dehydrated state.

CONCLUSION

Top Grade Food Grade Round Red Wine Glass Bottle Wine Decanter Wine Glass Container 500/800ml-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.PVC Skirt Pop-up Speakers Indoor Massage Portable Hot Tub.

ACKNOWLEDGMENTS

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

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KOMATZU, H.; SAITO, H.; OKADA, S.; TANAKA, M.; EGASHIRA, M.; HANDA, T.Lightweight Double Zipper Black Leather Wash Bag Toiletry Kit Pouch-dried small liposomes in the presence of maltose. Chem. Phys. Lipids,Amsterdam, v.113, p.29-39, 2001.[Plastic Stapler Office Stapler Book Stapler 213]

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LASIC, D.D. Recent developments in medical applications of liposomes: sterically stabilized liposomes in cancer therapy and gene deliveryin vivo. J. Control. Rel.,Amsterdam, v.48, p.203-22. 1997.[Kickstand and Holster Belt Clip Combo Holster Mobile Phone Case Cover for Alcatel Pixi 3 (5) /5015/5010]

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LIMA, E.M.; LOPES, L.B.;Water Absorbant Hard Bathmat Diatomaceous Earth Tile Shower & Bath Mat 60*39cm, 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.[Interior PVC Wall Cladding Panels for Shower Room]

LIMA, E.M.; OLIVEIRA, A.G.Hot Sale Brass / Zinc Shattaf Hand Held Bidet Sprayery2330).Drug Dev. Ind. Pharm.,New York, v.28, p.673-680, 2002.[Wholesale PE/LDPE Custom Printing Shopping Plastic Bags with Own Logo]

LOPES, L.B.;Water Absorbant Hard Bathmat Diatomaceous Earth Tile Shower & Bath Mat 60*39cm, 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.[Calcium Hypochlorite 70% of Granular Form]

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.[60-6000kw Hot Sale Customized Energy Saving Kgps Series Power Supply for Melting Furnace]

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.[Wholesale Supply Brand Fashion Light Safety Shoes]

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NEW, R.R.C.Liposomes:a practical approach.Oxford: IRL Press, 1997. p. 33-161.[2.5 Inch 3W LED Downlight C-Tick SAA CE RoHS 3year Warranty]

RADES, T.; MÜLLER-GOYMANN, C.C.New Professional Eyeshadow Brushes Set Lip Cosmetic Brush.Int. J. Pharm.,Amsterdam, v.159, p. 215-222, 1997.[Shinning Bridal Wedding Silver Crystal Hair Comb]

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

Colorful Felt iPad/Laptop Bag Wholesale Felt BagsCorrespondence:
A.G. Oliveira
Departamento de Fármacos e Medicamentos
Faculdade de Ciências Farmacêuticas
Rodovia Araraquara-Jaú km 01
14801-902 – Araraquara-SP-Domestic Surface Electric Water Pump (0.75kw/1HP) Qb80
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