SOLID LIPID NANOPARTICLE ppt
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Transcript of SOLID LIPID NANOPARTICLE ppt
ANWESHA DANDAPATH
M.PHARM,1st YEAR,2nd SEMESTER
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
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
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
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
LIPIDS SURFACTANTS
TriglyceridesTricaprinTrimyristinTrilaurinHard fat types witepsolO W35witepsolO H35Acyl glycerolGlyceryl monostearateGlyceryl monooleateWaxesFatty acidsCetyl palmitateFatty acidsStearic acid
PhospholipidsSoy lecithinEgg lecithinEthylene oxide/propylene oxide copolymersPolyoxamer188Polyoxamer407Sorbitan ethylene oxide/propylene oxide co polymerPolysorbate20Polysorbate60Polysorbate80Bile saltsSodium cholateSodium glycholate
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%)
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
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
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
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
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
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)
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
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.
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
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
DIFFERENT TYPES These are
HOMOGENOUSMATRIX
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 phaseUpon cooling ,the lipid precipitates first ,forming a drug free lipid coreDrug reprecipitates in the remaining liquid lipid phase Increase in drug concentration in the outer shellCrystallization of drug enriched shelle.g. Tetracycline SLN
Cooling of the formed nanoemulsion will lead to supersaturation of drug in melted lipidIt leads to drug precipitation prior to lipid precipitationFurther cooling leads to precipitation of lipid surrounding the drug enriched core.
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
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.
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)
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
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
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
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
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
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(alkylcyanoacrylate) nanoparticles with anticancer agents ,oligonucleotides
2. Poly(alkylcyanoacrylate) polyester nanoparticles with anti parasistic or anti viral agents
3. Polyesters with adsorbed polyethylene glycols or pluronics or derivatized polyesters
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