Dispersion Es

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  • Disperse SystemsSVIPS-TPG

  • IntroductionDisperse systems fall into two categoriesEmulsionsSuspensions In addition, pharmaceutical products contain API, which may be solid or liquid, uniformly dispersed into the emulsion or dispersion baseHence, many types and variations of mixing, dispersion, emulsification and size reduction equipments can be used to prepare disperse systemsSVIPS-TPG

  • Factors influence selection processSuspensionViscosityDensityParticle shape, size and size distributionEmulsionSurface tensionChemical activity of liquid phasesSurfactantsStabilizers

  • ParametersRelationship of Mixing equipment to viscosityA large no. of dispersed products exhibitPlasticityPseudo plasticityThixotropyMacroscale versus Microscale mixingMacroscale mixing refers to adequate flow in all areas of mixing vessel (also called as blending)In microscale mixing individual components are mixed

  • Mixer power equation P = C.[ ND2 /]-a .[ N2 D /g]-b N3D5 WhereP= power consumedD= impeller diameterN= speed of rotationg= acceleration due to gravity= liquid density= viscositya & b = exponents determined experimentally C= proportionality constant[ ND2 /] = Reynolds number, [ N2 D /g] = Frounde numberWhen flow is laminar , a is close to 1 & b is close to zeroWhen flow is turbulent both the exponents are close to zero

  • MethodsBlending of miscible liquidsSuspension of solids Dispersion of solids (size reduction)/ emulsificationEmulsification of immiscible liquid systemsPreparation of liposomesScale upVacuum processing

  • Scale upScale up ratio = large scale production rate small scale production rate

    Scale up ratio 10 to 100 for laboratory to pilot and 10 to 200 for pilot plant to commercial production

  • Scale up parameters Power PP/V ratio= power consumed/ vol. of VesselTip speed of impeller = DNPumping rate per unit volume, Q/V Pumping rate Q ND3 Geometric, kinetic and dynamic similarity

  • Scale upFor dispersions, the controlling factor is often tip speed, which determines the maximum shear rates.Never use laboratory scale or pilot scale equipment that can not be built or operated in larger sizesOptimization of scale up around only one parameter is not usually feasible. Some compromises are normally necessary

  • Vacuum processingPresence of dispersed air is almost a detrimental factor to emulsion stabilityAll mixing steps should be conducted to incorporate least amount of airOne way of combating the aeration problems is to perform the entire process in a vacuumVacuum processing also allows the option of drawing powders into batch from the bottom outlet. This promotes immediate dispersionFoam may form even during processing under vacuum.

  • Steps to prevent foam formationGentle mixing is best for initial deaeration stepIncrease the absolute pressure (decreasing the vacuum) outside of the foam bubble to crush bubbleBy increasing and then decrease in the vacuum, the batch can be deaeratedDevices are available for deaeration on continuous basis.

  • Mixing equipmentA. MixersB. High speed dispersersC. Rotor stator mixersD. Combination mixersE. In- line mixersF. Non- mechanical disperse processingG. Fine suspension and size reduction equipment

  • Mixing equipmentA. MixersPropeller mixersTurbine mixersAnchor mixersScraped surface agitatorsCounter rotation

  • B. High speed DispersersDesign: Also called as saw blade disperserThis machine consists of a variable speed shaft connected to an impeller with a serrated edgeThe tip speed is set around 4000 ft/minThe diameter of impeller should be 1/3 of diameter of vesselThe impeller should be located one impeller diameter off the bottom of vesselApplication: This is used to disperse pigments into liquidsLimitation: The high speed disperse design is ineffective if the viscosity is lowSuitable for suspensions not emulsionsAir incorporation is another problem

  • C. Rotor/ stator mixerRadial flow with statorRotating stator: In this both impeller and the stator both rotate on drive shaft and hence produce combined shearHence no supporting rod necessary and no steady bearing is required Axial flow rotor/ stator mixer

  • D. Combination MixersAnchor plus Rotor/ statorAnchor plus high speed disperser

  • In line MixersRotor/stator mixer disperser emulsifiersColloid millsPiston homogenizersUltrasonic vibrating homogenizerMicro fluidizer technologyLow pressure cyclone emulsifiersStatic mixers: pipe line mixers contain series of baffles in a cylindrical pipe

  • Microfluidizer Technologies This device uses a high pressure positive displacement pump operating at pressure 500-20000 psig through interaction chamber.The interaction chamber consists of microchannels as narrow as 50 microns and cause the flow of product to occur as very thin sheetsMicrochannels are Y- shaped divides flow into two micro streamsAt the impingement area the collision of two high speed flow streams in a very tight spot creates various droplet size reductions and mixingThis technology is used to prepare unilamellar liposomes and micro emulsions

  • F. Non mechanical disperse processingCritical fluids liposome processSuper critical or near critical fluids are gases CO2 and propane under ambient conditionsWhen compressed at conditions above their critical temperature and pressure, these substances become fluids with liquid like density and gas like properties of low viscosity and high diffusivity.The gaseous characteristics increase mass transfer rate, thereby decrease processing timeA circulating pump operating in a high pressure loop ensures good mixing between the supercritical fluids and the liposomal raw materialsAfter specified residence time, the resulting mixture is trough the dip tube with its nozzle in a decompression chamber that contains aqueous solution or fine dispersion of drug for liposomal encapsulation.

  • Fine suspension and size reduction equipmentThree roll millsBall mills or jar millsContinuous stirred media mills

  • Three roll millsCapable of dispersing small tightly bound agglomerates and hard discrete particlesPremixed suspension allowed to travel between rotating rolls that are located about 10- 50 microns apart.The particles not only subject to very high shear mechanical crushing and smearing Three rolls are named as feed roll, center roll and apron roll

  • Three roll millsThe shear rates in a three roll mill are a function ofThe roll radius, R inchesThe difference in rpm of the rolls in contact, rpmClearance between the rolls known as nip clearance, z (mils)Shear rate, = 105R /z

  • Ball millFor true size reduction of fine particles or for deagglomeration of very tightly bound agglomeratesSmall version of ball mill is known as jar mill Disadvantage is time consuming processFor difficult to grind materials, ball mill is still the machine of choice

  • Agitated bead millsJust like ball mill ,the bead mill uses a charge of inert small balls around 2-8mm in diameterIf the beads are ceramic media millIf the beads are steel balls- shot millLarge grains of sand(3mm)- sand millThe cylinder is either horizontal or verticalNot often used in ph. industry, except when particle size requirements fall below 10 microns

  • ReferencesDisperse systems,vol-1 to 3Remingtons pharmaceutical sciencesAnsels pharmaceutical dosage formsDispencing pharmacy by cooper and gunn THAN-Q-U