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SOLID LIPID NANOPARTICLE ppt

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This presentation covers a brief information about SOLID LIPID NANOPARTICLE

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SOLID LIPID NANOPARTICLE ppt

  1. 1. ANWESHA DANDAPATH M.PHARM,1st YEAR,2nd SEMESTER
  2. 2.  INTRODUCTION  SLN OVER EMULSION & LIPOSOME  SOLID LIPID AS MATRIX MATERIAL  LIST OF EXCIPIENTS USED IN SLN PREPARATION  ADVANTAGES & DISADVANTAGES  METHODS OF PREPARATION  DRUG RELEASE  CHARACTERIZATION OF SLN  PURIFICATION OF SLN  STEALTH SLN  APPLICATION
  3. 3.  SLN ARE  Colloidal carrier system(1- 100nm) Composed of a high melting point lipid as a solid core & coated by aqueous surfactant. Made up of drugs usually of BCS class п & ІV
  4. 4.  Lipid emulsion contain a neutral lipophilic core surrounded by a monolayer of amphiphilic lipid.  Liposome contain an outer bilayer of amphilphilic molecule such as phospholipid with an aqueous compartment inside.  SLN contain a solid lipid core surrounded by phospholipid
  5. 5.  The term lipid in broad sense includes triglycerides ,partial glycerides ,fatty acids , fats & waxes. ADVANTAGES OF SOLID LIPID OVER LIQUID LIPID 1)Mobility of reactive agents in a solid matrix is lower than in a liquid matrix .so that the rate of chemical degradation reactions may be regarded. 2)Micro phase seperations of the active ingredients & carrier lipid within the individual liquid particles can be controlled, thereby preventing the accumulation of active compounds at the surface of lipid particles where chemical degradation often occurs 3)The absorption of poorly absorbed bio active compounds has been shown to be increased after incorporation into solid lipid nanoparticle
  6. 6. LIPIDS SURFACTANTS Triglycerides Tricaprin Trimyristin Trilaurin Hard fat types witepsolO W35 witepsolO H35 Acyl glycerol Glyceryl monostearate Glyceryl monooleate Waxes Fatty acids Cetyl palmitate Fatty acids Stearic acid Phospholipids Soy lecithin Egg lecithin Ethylene oxide/propylene oxide copolymers Polyoxamer188 Polyoxamer407 Sorbitan ethylene oxide/propylene oxide co polymer Polysorbate20 Polysorbate60 Polysorbate80 Bile salts Sodium cholate Sodium glycholate
  7. 7.  Use of biodegradable physiological lipids which decreases the danger of acute and chronic toxicity and avoidance of organic solvents in production method.  Improved bioavailability of poorly water soluble molecules  Site specific delivery of drugs, enhanced drug penetration into the skin via dermal application  Chemical protection of labile incorporated compound.  Large scale production is possible  Long term stability DISADVANTAGES  Poor loading capacity  Drug expulsion after polymeric transition during storage  Relatively high water content of the dispersions(70%-90%)
  8. 8.  THERE ARE SEVERAL METHODS FOR PREPARATION OF SLN.THOSE ARE: 1)HOT HOMOGENIZATION TECHNIQUE 2)COLD HOMOGENIZATION TECHNIQUE 3)ULTRASONICATION OR HIGH SPEED HOMOGENIZATION 4)SOLVENT EMULSIFICATION-EVAPORATIO TECHNIQUE 5)SOLVENT EMULSIFICATION –DIFFUSION TECHNIQUE 6)MICRO EMULSION BASED METHOD 7)SUPERCRITICAL FLUID TECHNOOGY a)IGA/SAS b)PGSS 8)DOUBLE EMULSION TECHNIQUE 9)MEMBRANE CONTACTOR TECHNIQUE 8)SOLVENT INJECTION TECHNIQUE
  9. 9. SOLIDIFICATION OF THE NANO EMULSION BY COOLING DOWN TO ROOM TEMPERATURE TO FORM SLN O/W –NANO EMULSION HIGH PRESSURE HOMOGENIZATION AT A TEMPERATURE ABOVE THE LIPID MELTING POINT PREMIX USING A STIRRER TO FORM A COARSE PRE EMULSION MIXING OF THE PREHEATED DISPERSION MEDIUM AND DRUG LIPID MELT DISSOLUTION OF THE DRUG IN THE MELTED LIPID MELTING OF THE LIPID
  10. 10. SOLID LIPID NANOPARTICLES DISPERSION OF THE LIPID IN THE COLD AQUEOUS DISPERSION MEDIUM GRINDING IN A POWDER MILL(50-100 MICROMETER PARTICLES) SOLIDIFICATION OF THE DRUG LOADED LIPID IN LIQUID NITROGEN OR DRY ICE DISSOLUTION/SOLUBILIZATION OF THE DRUG IN THE MELTED LIPID MELTING OF THE LIPID
  11. 11.  ADVANTAGES: a)Low capital cost b)Demonstrated at lab scale DISADVANTAGES: a)Energy intensive process b)Demonstrated at lab scale bimolecular damage c)Polydisperse distribution d)Unproven scalability
  12. 12. 1)Drug is added to previously melt solid lipid. 2)The heated aqueous phase (heated to same temperature) is added to the melted lipid . 3)Emulsified by probe sonication or by using high speed stirrer or aqueous phase added to lipid phase drop by drop followed by magnetic stirring 4)The obtained pre emulsion is then ultrasonicated using probe sonicator with water bath(0◦). In order to avoid recrystallization during the process the production temperature kept at least 5◦ C above the lipid melting point. 5)Emulsion is filtered through a .45 micrometer in order to remove inpurities carried in during sonication 6)SLN are produced and is stored at low temperature
  13. 13. Precipitate of SLN is formed Coarse emulsion is passed through microfluidizer & organic solvent is being evaporated at room temperature under reduced pressure(e.g.rotary evaporator) Emulsified in an aqueous phase using high speed homogenizer Lipophilic material & hydrophobic drug are dissolved in a water immiscible organic solvent(e.g.cyclohexane,toluene,chloroform)
  14. 14.  The solvent used(e.g. benzyl alcohol, butyl lactate) in this technique is partially miscible with water and this technique can be carried out either in aqueous phase or in oil.  Initially ,both the solvent and water are mutually saturated in order ensure the initial thermodynamic eqillibrium of both liquid  Heating is required to solubilize the lipid ,the saturationship was performed at that temperature
  15. 15.  STEPS: a)The lipid & drugs were dissolved in water saturated solvent  b) organic phase was emulsified with solvent saturated aqueous solution containing the stabilizer  c)Formation of o/w emulsion  d)Water in typical ratio ranges 1:5 to 1:10 were added to the system in order to allow solvent diffusion into the continuous phase  e) Aggregation of the lipid in nanoparticles.
  16. 16.  Liquid phase was pressed at a temperature above the melting point of the lipid through the membrane pore allowing the formation of small droplets.  The aqueous phase was stirred continuously and circulates tangentially inside the membrane module & sweeps away the droplets being formed  SLN were prepared after cooling at room temperature  B=tangential flow of the aqueous phase  A=lipid phase, permeation under applied pressure
  17. 17.  There are mainly 3 drug incorporation models which describe the incorporation of drug into SLN 1)Homogenous matrix model 2)Drug enriched shell ,core shell model 3)Drug enriched core ,core shell model
  18. 18. DIFFERENT TYPES  These are HOMOGENOUS MATRIX DRUG ENRICHED SHELL WITH LIPID CORE DRUG ENRICHED CORE WITH LIPID SHELL  Obtained by incorporating highly lipophilic drugs into SLN using hot homogenization technique or cold homogenization technique.  e.g. etomidate SLN Obtained during the production ,when the drug partitioned to water phase Upon cooling ,the lipid precipitates first ,forming a drug free lipid core Drug reprecipitates in the remaining liquid lipid phase Increase in drug concentration in the outer shell Crystallization of drug enriched shell e.g. Tetracycline SLN Cooling of the formed nanoemulsion will lead to supersaturation of drug in melted lipid It leads to drug precipitation prior to lipid precipitation Further cooling leads to precipitation of lipid surrounding the drug enriched core.
  19. 19.  Parameters used for characterization are Particle size & size distribution Charge determination Surface hydrophobicity Chemical analysis of surface Carrier drug interaction Nanoparticle dispersion stability Release profile Drug stability
  20. 20. PHOTON CORRELATION SPECTROSCOPY: Suitable for particle size in the range of 3nm-3mm. Method is based on the dynamic scattering of laser light due to Brownian motion.  ELECTRON MICROSCOPY: Measures individual paticles for size & its distribution Transmission electron microscopy(TEM):Uses electrons transmitted through the sample. Permits differentiation among nanocapsules & emulsion droplets Scanning electron microscopy(SEM):Uses electrons transmitted from the surface of the sample Atomic force microscopy(AFM):Measures the force acting between surface of the sample and tip of the probe.
  21. 21. 2)DENSITY:  Helium or air using a gas pycnometer  Density gradient centrifugation 3)Molecular weight: Gel permeation chromatography by using a refractive index detector 4)Specific surface area: specific surface area is determined by sorptometer specific surface area=6/(Density*Diameter of the particle)
  22. 22. SURFACE HYDROPHOBICITY: Regulates the extent & type of hydrophobic interactions of SLN with blood components & determines its biofate. METHODS: 1. Hydrophobic interaction chromatography 2. Rose bengal(dye) binding 3. Water contact angle measurements SURFACE CHARGE & ELECTRONIC MOBILITY: 1. Laser doppler anemometry 2. Zeta potentiometer
  23. 23. INVITRO RELEASE: 1. Dialysis technique 2. Ultrafiltration technique NANOPARTICLE YIELD: %Yield=(Actual weight of the product/total weight of drug & excipient) %Drug Entrapment=(mass of the drug in nanoparticles/Mass of the drug used in formulation)*100 DRUG STABILITY: Bioassay of the drug extracted from nanoparticles Chemical ananlysis of the drug
  24. 24.  There are 3 laboratory scale method of purification. These are GEL FILTRATION • REMARKS: • High molecular weight substances & impurities are difficult to remove DIALYSIS • REMARKS: • Time consuming process • Scaling up is difficult • High molecular weight substances are difficult to remove ULTRA- CENTRIFUGATION •RE •R • REMARKS • Aggregation of the particle • Time consuming process
  25. 25.  INDUSTRIAL STAND POINT METHOD: Known as cross fitration method Nano particle suspension is filtered through membrane,with the direction of the fluid being tangential to the surface of he membrane Clogging is avoided
  26. 26.  STEALTH SLNs are one kind of shielded SLN , produced to avoid opsonization & to prolong circulation lifetime  The hydrophilic & flexible polymer coating on SLN is thought mask the surface from opsonins. STEALTHING AGENTS: 1. Dipalmitoyl phosphatidylethanolamine-PEG-2000 2. Stearic acid-PEG2000 3. Polyoxamer PEG-2000 represents hydrophilic part & long PEG form hydrophilic cloud over SLN & protect the nanoparticle by steric repulsion or lowering protein adsorption
  27. 27. APPLICATION PURPOSE MATERIAL 1. Cancer therapy 2. Intracellular tergating 3. Prolonged systemic circulation 1. Targeting ,reduced toxicity, enhanced uptake of anti cancer drug, improved in vitro & in vivo stability 2. Target reticulo endothelial systems for intracellular infections 3. Prolonged systemic drug effect ,avoid uptake by reticuloendothelial system 1. Poly(alkylcyanoacryla te) nanoparticles with anticancer agents ,oligonucleotides 2. Poly(alkylcyanoacryla te) polyester nanoparticles with anti parasistic or anti viral agents 3. Polyesters with adsorbed polyethylene glycols or pluronics or derivatized polyesters
  28. 28. APPLICATION* PURPOSE MATERIAL 4)Vaccine adjuvant 5)Peroral absorption 6)DNA Delivery 7)Oligonucleotide delivery 4)Enhances immune response ,alternate acceptable adjuvant 5)Enhanced bio availability ,protection from GI enzymes 6)Enhanced delivery & significantly higher expression level 7)Enhanced delivery of oligonucleotide 4)Poly(methyl methacrylate) nanoparticles with vaccines(oral & intramuscular immunization) 5)Poly (methylmethacrylate) nanoparticles with protein & therapeutic agents 6)DNA –gelatin nanoparticle, DNA – chitosan nanoparticle ,PDNA –(DL-lactide-co- glycolide) nanoparticle) 7)Alginate poly(D,L),Lactic acid nanoparticles

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