Liquid Liquid OralsOrals

2

Steps of liquid manufacturing processSteps of liquid manufacturing process

Planning of material requirements:Planning of material requirements:

Liquid preparation:Liquid preparation:

Filling and Packing:Filling and Packing:

Quality assurance:Quality assurance:

3

Critical aspects of liquid manufacturingCritical aspects of liquid manufacturing

Physical Plant:Physical Plant: Heating, ventilation and air controlling Heating, ventilation and air controlling

system:system: the effect of long processing times at the effect of long processing times at

suboptimal temperatures should be suboptimal temperatures should be considered in terms of consequences on considered in terms of consequences on the physical or chemical stability of the physical or chemical stability of ingredients as well as product.ingredients as well as product.

4

Solutions:Solutions:

Protecting the APIProtecting the API Buffers, antioxidants, Buffers, antioxidants, preservativespreservatives

Maintaining the Maintaining the appearanceappearance

Colorings, stabilizers, Colorings, stabilizers, cosolvents, cosolvents, antimicrobial antimicrobial preservativespreservatives

Taste/smell maskingTaste/smell masking Sweetners, flavorings.Sweetners, flavorings.

Formulation aspects of oral liquidsFormulation aspects of oral liquids

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SuspensionsSuspensions::

Purpose Purpose Agent Agent

Facilitating the connection Facilitating the connection between API and vehiclebetween API and vehicle

-wetting agents-wetting agents

Salt formation ingredientsSalt formation ingredients

Protecting the APIProtecting the API - Buffering-systems, - Buffering-systems, polymers, antioxidantspolymers, antioxidants

Maintaining the Maintaining the suspension appearancesuspension appearance

Colorings, suspending Colorings, suspending agent, flocculating agent.agent, flocculating agent.

Masking the unpleasant Masking the unpleasant taste/smell taste/smell

Sweeteners, flavoringsSweeteners, flavorings

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Emulsions:Emulsions:

Purpose Purpose AgentAgent

Particle SizeParticle Size Solid particles, Droplet Solid particles, Droplet particlesparticles

Protecting the APIProtecting the API Buffering-systems, Buffering-systems, antioxidants, polymersantioxidants, polymers

Maintaining the Maintaining the appearanceappearance

Colorings, Emulsifying Colorings, Emulsifying agents, Penetration agents, Penetration enhancers, gelling agentsenhancers, gelling agents

Taste/smell maskingTaste/smell masking Sweetners, flavoringsSweetners, flavorings

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Layout of the pilot plantLayout of the pilot plant

8

Equipments Equipments

MixerMixer

Homogenizer Homogenizer

Filteration assemblyFilteration assembly

Bottling assembly Bottling assembly

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Filtration assemblyFiltration assembly

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General flow chartGeneral flow chart

Raw Materials Measured and weighed

Mixing

Filling

Packing

Distilled water

Finished products storage

Quality Assurance

11

Quality assuranceQuality assurance

Dissolution of drugs in solutionDissolution of drugs in solution Potency of drugs in suspensionPotency of drugs in suspension Temperature uniformity in emulsionsTemperature uniformity in emulsions Microbiological controlMicrobiological control Product uniformityProduct uniformity Final volumeFinal volume Stability Stability

Disperse systems fall into two categoriesDisperse systems fall into two categories– EmulsionsEmulsions– Suspensions Suspensions

In addition, pharmaceutical products contain In addition, pharmaceutical products contain API, which may be solid or liquid, uniformly API, which may be solid or liquid, uniformly dispersed into the emulsion or dispersion basedispersed into the emulsion or dispersion base

Hence, many types and variations of mixing, Hence, many types and variations of mixing, dispersion, emulsification and size reduction dispersion, emulsification and size reduction equipments can be used to prepare disperse equipments can be used to prepare disperse systemssystems

Factors influence selection Factors influence selection processprocess

SuspensionSuspension– ViscosityViscosity– DensityDensity– Particle shape, size and size distributionParticle shape, size and size distribution

EmulsionEmulsion– Surface tensionSurface tension– Chemical activity of liquid phasesChemical activity of liquid phases– SurfactantsSurfactants– Stabilizers Stabilizers

ParametersParameters

Relationship of Mixing equipment to Relationship of Mixing equipment to viscosityviscosity– A large no. of dispersed products exhibitA large no. of dispersed products exhibit

PlasticityPlasticityPseudo plasticityPseudo plasticityThixotropyThixotropy

Macroscale versus Microscale mixingMacroscale versus Microscale mixing– Macroscale mixing refers to adequate Macroscale mixing refers to adequate

flow in all areas of mixing vessel (also flow in all areas of mixing vessel (also called as blending)called as blending)

– In microscale mixing individual In microscale mixing individual components are mixed components are mixed

Mixer power equationMixer power equation P P = C.[ = C.[ ρρNDND2 2 /ŋ]/ŋ]-a -a .[ .[ NN22 D D /g]/g]-b -b

ρρNN33DD55

WhereWhereP= power consumedP= power consumedD= impeller diameterD= impeller diameterN= speed of rotationN= speed of rotationg= acceleration due to gravityg= acceleration due to gravityρρ= liquid density= liquid densityŊ= viscosityŊ= viscositya & b = exponents determined experimentally a & b = exponents determined experimentally C= proportionality constantC= proportionality constant

[ [ ρρNDND2 2 /ŋ] = Reynolds number, /ŋ] = Reynolds number, [ [ NN22 D D /g] = Frounde /g] = Frounde numbernumber

When flow is laminar , a is close to 1 & b is close to zeroWhen flow is laminar , a is close to 1 & b is close to zeroWhen flow is turbulent both the exponents are close to When flow is turbulent both the exponents are close to

zerozero

MethodsMethods

Blending of miscible liquidsBlending of miscible liquids Suspension of solids Suspension of solids Dispersion of solids (size reduction)/ Dispersion of solids (size reduction)/

emulsificationemulsification Emulsification of immiscible liquid Emulsification of immiscible liquid

systemssystems Preparation of liposomesPreparation of liposomes Scale upScale up Vacuum processingVacuum processing

Scale upScale up

Scale up ratio = Scale up ratio = large scale production rate large scale production rate

small scale production ratesmall scale production rate

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

Scale up parameters Scale up parameters

Power PPower P P/V ratio= power consumed/ vol. of P/V ratio= power consumed/ vol. of

VesselVessel Tip speed of impeller = Tip speed of impeller = ππDNDN Pumping rate per unit volume, Q/V Pumping rate per unit volume, Q/V Pumping rate Q Pumping rate Q αα ND ND3 3

Geometric, kinetic and dynamic Geometric, kinetic and dynamic similaritysimilarity

Scale upScale up

For dispersions, the controlling factor is For dispersions, the controlling factor is often tip speed, which determines the often tip speed, which determines the maximum shear rates.maximum shear rates.

Never use laboratory scale or pilot scale Never use laboratory scale or pilot scale equipment that can not be built or equipment that can not be built or operated in larger sizesoperated in larger sizes

Optimization of scale up around only one Optimization of scale up around only one parameter is not usually feasible. Some parameter is not usually feasible. Some compromises are normally necessarycompromises are normally necessary

Vacuum processingVacuum processing Presence of dispersed air is almost a Presence of dispersed air is almost a

detrimental factor to emulsion stabilitydetrimental factor to emulsion stability All mixing steps should be conducted to All mixing steps should be conducted to

incorporate least amount of airincorporate least amount of air One way of combating the aeration problems One way of combating the aeration problems

is to perform the entire process in a vacuumis to perform the entire process in a vacuum Vacuum processing also allows the option of Vacuum processing also allows the option of

drawing powders into batch from the bottom drawing powders into batch from the bottom outlet. This promotes immediate dispersionoutlet. This promotes immediate dispersion

Foam may form even during processing Foam may form even during processing under vacuum. under vacuum.

Steps to prevent foam formationSteps to prevent foam formation

Gentle mixing is best for initial Gentle mixing is best for initial deaeration stepdeaeration step

Increase the absolute pressure Increase the absolute pressure (decreasing the vacuum) outside of (decreasing the vacuum) outside of the foam bubble to crush bubblethe foam bubble to crush bubble

By increasing and then decrease in By increasing and then decrease in the vacuum, the batch can be the vacuum, the batch can be deaerateddeaerated

Devices are available for deaeration Devices are available for deaeration on continuous basis.on continuous basis.

Mixing equipmentMixing equipment

A. MixersA. Mixers

B. High speed dispersersB. High speed dispersers

C. Rotor stator mixersC. Rotor stator mixers

D. Combination mixersD. Combination mixers

E. In- line mixersE. In- line mixers

F. Non- mechanical disperse processingF. Non- mechanical disperse processing

G. Fine suspension and size reduction G. Fine suspension and size reduction equipmentequipment

Mixing equipmentMixing equipment

A. MixersA. Mixers Propeller mixersPropeller mixers Turbine mixersTurbine mixers Anchor mixersAnchor mixers Scraped surface agitatorsScraped surface agitators Counter rotationCounter rotation

High shear mixerHigh shear mixer A A high shear mixerhigh shear mixer disperses, or transports, one phase disperses, or transports, one phase

into a main continuous phase which would normally be into a main continuous phase which would normally be immiscibleimmiscible. .

A rotor or impellor, together with a stationary component A rotor or impellor, together with a stationary component known as a stator, or an array of rotors and stators, is known as a stator, or an array of rotors and stators, is used either in a tank containing the solution to be mixed, used either in a tank containing the solution to be mixed, or in a pipe through which the solution passes, to create or in a pipe through which the solution passes, to create shearshear. A high shear mixer can be used to create . A high shear mixer can be used to create emulsions, suspensions, lyosols (gas dispersed in liquid) emulsions, suspensions, lyosols (gas dispersed in liquid) and granular products. and granular products.

It is used in the adhesives, chemical, cosmetic, food It is used in the adhesives, chemical, cosmetic, food pharmaceutical and plastics industries for emulsification, pharmaceutical and plastics industries for emulsification, homogenization, particle size reduction and dispersion.homogenization, particle size reduction and dispersion.

How it worksHow it works

Fluid undergoes shear when one area of fluid Fluid undergoes shear when one area of fluid travels with a different velocity relative to an travels with a different velocity relative to an adjacent area. adjacent area.

A high shear mixer uses a rotating impeller or A high shear mixer uses a rotating impeller or high speed rotor, or a series of such impellers high speed rotor, or a series of such impellers or inline rotors, usually powered by an electric or inline rotors, usually powered by an electric motor, to "work" the fluid, creating flow and motor, to "work" the fluid, creating flow and shear. shear.

The velocity, or tip speed of the fluid at the The velocity, or tip speed of the fluid at the outside diameter of the rotor will be higher outside diameter of the rotor will be higher than the velocity at the centre of the rotor, than the velocity at the centre of the rotor, and it is this that creates shear.and it is this that creates shear.

Cont…Cont…

A stationary component may be used in A stationary component may be used in combination with the rotor and is referred to as combination with the rotor and is referred to as the stator. The stator creates a close clearance the stator. The stator creates a close clearance gap between the rotor and itself and forms an gap between the rotor and itself and forms an extremely high shear zone for the material as it extremely high shear zone for the material as it exits the rotor. exits the rotor.

The rotor and stator combined together are The rotor and stator combined together are often referred to as the mixing head, or often referred to as the mixing head, or generator. A large high shear rotor-stator mixer generator. A large high shear rotor-stator mixer may contain a number of generators.may contain a number of generators.

Key design factors include;Key design factors include;

The diameter of the rotor and its rotational The diameter of the rotor and its rotational speed, speed,

The distance between the rotor and the The distance between the rotor and the stator, stator,

The time in the mixer, and The time in the mixer, and The number of generators in the series.The number of generators in the series.

Variables include the number of rows of Variables include the number of rows of teeth, their angle, and the width of the teeth, their angle, and the width of the openings between teeth.openings between teeth.

Cont…Cont…

Batch high shear mixersBatch high shear mixers The components to be mixed (whether immiscible The components to be mixed (whether immiscible

liquids or powder in liquid) are fed from the top into liquids or powder in liquid) are fed from the top into a mixing tank containing the mixer on a rotating a mixing tank containing the mixer on a rotating shaft at the bottom of the tank. shaft at the bottom of the tank.

A batch high shear mixer can process a given A batch high shear mixer can process a given volume of material approximately twice as fast as an volume of material approximately twice as fast as an inline rotor-stator mixer of the same power rating, inline rotor-stator mixer of the same power rating, and continue to be used where faster processing by and continue to be used where faster processing by volume is the major requirement, and space is not volume is the major requirement, and space is not limited.limited.

Some high shear mixers are designed to run dry, Some high shear mixers are designed to run dry, limiting the amount of cleaning needed in the tank limiting the amount of cleaning needed in the tank When used sticky solutions.When used sticky solutions.

Inline high shear mixersInline high shear mixers In rotor-stator mixer, the rotor-stator array is In rotor-stator mixer, the rotor-stator array is

contained in a housing with an inlet at one end and contained in a housing with an inlet at one end and an outlet at the other, and the rotor driven through a an outlet at the other, and the rotor driven through a seal. The components to be mixed are drawn seal. The components to be mixed are drawn through the generator array in a continuous stream, through the generator array in a continuous stream, with the whole acting as a centrifugal pumping with the whole acting as a centrifugal pumping device. device.

Inline high shear mixers offer a more controlled Inline high shear mixers offer a more controlled mixing environment, take up less space, and can be mixing environment, take up less space, and can be used as part of a continuous process. used as part of a continuous process.

Equilibrium mixing can be achieved by passing the Equilibrium mixing can be achieved by passing the product through the inline high shear mixer more product through the inline high shear mixer more than once.than once.

When used with a vacuum pump & hopper, an When used with a vacuum pump & hopper, an Inline Shear Mixer can be a great way to Inline Shear Mixer can be a great way to incorporate powders into liquid streams. incorporate powders into liquid streams. Otherwise known as High Shear Powder Inductors, Otherwise known as High Shear Powder Inductors, these systems are a great way of keeping the these systems are a great way of keeping the process on the floor level instead of working with process on the floor level instead of working with heavy bags on mezzanines.heavy bags on mezzanines.

High Shear Powder Induction systems also offer High Shear Powder Induction systems also offer easy interchangeability with multiple tanks.easy interchangeability with multiple tanks.

Cont…Cont…

High shear granulatorsHigh shear granulators

A high shear granulator is a process array A high shear granulator is a process array consisting of an inline or batch high shear consisting of an inline or batch high shear mixer and a fluid bed dryer. mixer and a fluid bed dryer.

In a granulation process, only the solid In a granulation process, only the solid component of the mixture is required. component of the mixture is required.

Fluid is used only as an aid to processing. Fluid is used only as an aid to processing. The high shear mixer processes the solid The high shear mixer processes the solid

material down to the desired particle size, material down to the desired particle size, and the mixture is then pumped to the drying and the mixture is then pumped to the drying bed where the fluid is removed, leaving bed where the fluid is removed, leaving behind the granular productbehind the granular product

Ultra high shear inline mixersUltra high shear inline mixers The high shear mixing takes place in a single or The high shear mixing takes place in a single or

multiple passes through a rotor-stator array. The multiple passes through a rotor-stator array. The mixer is designed to subject the product to higher mixer is designed to subject the product to higher shear and a larger number of shearing events than a shear and a larger number of shearing events than a standard inline rotor-stator mixer, producing an standard inline rotor-stator mixer, producing an exceptionally narrow particle size distribution. Sub exceptionally narrow particle size distribution. Sub micrometre particle sizes are possible using the Ultra micrometre particle sizes are possible using the Ultra High Shear technology.High Shear technology.

To achieve this, the machine is equipped with stators To achieve this, the machine is equipped with stators with precision machined holes or slots through which with precision machined holes or slots through which the product is forced by the rotors.the product is forced by the rotors.

The mechanism whereby the momentum of the flow The mechanism whereby the momentum of the flow is changed (for example by forcing it sideways is changed (for example by forcing it sideways through the stator), allowing for more processing in through the stator), allowing for more processing in a single passa single pass

Equilibrium mixingEquilibrium mixing High shear mixers are used in industry to produce High shear mixers are used in industry to produce

standard mixtures of ingredients that do not standard mixtures of ingredients that do not naturally mix. naturally mix.

When the total fluid is composed of two or more When the total fluid is composed of two or more liquids, the final result is lyosol. liquids, the final result is lyosol.

Each class may or may not be Each class may or may not be homogenizedhomogenized, , depending on the amount of input energy.depending on the amount of input energy.

To achieve a standard mix, the technique of To achieve a standard mix, the technique of equilibrium mixing is used. equilibrium mixing is used.

A target characteristic is identified, such that once A target characteristic is identified, such that once the mixed product has acquired that characteristic, it the mixed product has acquired that characteristic, it will not change significantly thereafter, no matter will not change significantly thereafter, no matter how long the product is processed. how long the product is processed.

For dispersions, this is the equilibrium particle For dispersions, this is the equilibrium particle size. For emulsions, it is the equilibrium size. For emulsions, it is the equilibrium droplet size. The amount of mixing required droplet size. The amount of mixing required to achieve equilibrium mixing is measured in to achieve equilibrium mixing is measured in tank turnover - the number of times the tank turnover - the number of times the volume of material must pass through the volume of material must pass through the high shear zone.high shear zone.

Cont…Cont…

Uses of high shear mixing Uses of high shear mixing technologytechnology

High shear mixers are used throughout the High shear mixers are used throughout the chemical process industries, wherever it is chemical process industries, wherever it is necessary to produce standardized mixtures of necessary to produce standardized mixtures of ingredients that do not naturally mix. ingredients that do not naturally mix.

These includeThese include PharmaceuticalsPharmaceuticals, preparations of suspensions and , preparations of suspensions and

granular productsgranular products PaperPaper manufacture, bleaching and preparation of manufacture, bleaching and preparation of

paper pulppaper pulp..

Food preparation, emulsions for sauces and Food preparation, emulsions for sauces and dressingsdressings..

Manufacture of Manufacture of cosmeticscosmetics and and toiletriestoiletries..

High speed DispersersHigh speed DispersersDesign: Also called as saw blade disperserDesign: Also called as saw blade disperser

This machine consists of a variable speed shaft This machine consists of a variable speed shaft connected to an impeller with a serrated edgeconnected to an impeller with a serrated edge

The tip speed is set around 4000 ft/minThe tip speed is set around 4000 ft/min The diameter of impeller should be 1/3 of diameter The diameter of impeller should be 1/3 of diameter

of vesselof vessel The impeller should be located one impeller The impeller should be located one impeller

diameter off the bottom of vesseldiameter off the bottom of vesselApplication: This is used to disperse pigments into Application: This is used to disperse pigments into

liquidsliquidsLimitation: The high speed disperse design is Limitation: The high speed disperse design is

ineffective if the viscosity is lowineffective if the viscosity is low Suitable for suspensions not emulsionsSuitable for suspensions not emulsions Air incorporation is another problemAir incorporation is another problem

Rotor/ stator mixerRotor/ stator mixer Radial flow with statorRadial flow with stator Rotating stator: Rotating stator:

– In this both impeller and the stator both In this both impeller and the stator both rotate on drive shaft and hence produce rotate on drive shaft and hence produce combined shearcombined shear

– Hence no supporting rod necessary and Hence no supporting rod necessary and no steady bearing is required no steady bearing is required

Axial flow rotor/ stator mixerAxial flow rotor/ stator mixer

Combination MixersCombination Mixers

Anchor plus Rotor/ statorAnchor plus Rotor/ stator Anchor plus high speed disperserAnchor plus high speed disperser

In line MixersIn line Mixers

Rotor/stator mixer disperser emulsifiersRotor/stator mixer disperser emulsifiers Colloid millsColloid mills Piston homogenizersPiston homogenizers Ultrasonic vibrating homogenizerUltrasonic vibrating homogenizer Micro fluidizer technologyMicro fluidizer technology Low pressure cyclone emulsifiersLow pressure cyclone emulsifiers Static mixers: pipe line mixers contain Static mixers: pipe line mixers contain

series of baffles in a cylindrical pipeseries of baffles in a cylindrical pipe

Microfluidizer Technologies Microfluidizer Technologies

This device uses a high pressure positive This device uses a high pressure positive displacement pump operating at pressure 500-20000 displacement pump operating at pressure 500-20000 psig through interaction chamber.psig through interaction chamber.

The interaction chamber consists of microchannels The interaction chamber consists of microchannels as narrow as 50 microns and cause the flow of as narrow as 50 microns and cause the flow of product to occur as very thin sheetsproduct to occur as very thin sheets

Microchannels are Y- shaped divides flow into two Microchannels are Y- shaped divides flow into two micro streamsmicro streams

At the impingement area the collision of two high At the impingement area the collision of two high speed flow streams in a very tight spot creates speed flow streams in a very tight spot creates various droplet size reductions and mixingvarious droplet size reductions and mixing

This technology is used to prepare unilamellar This technology is used to prepare unilamellar liposomes and micro emulsionsliposomes and micro emulsions

F. Non mechanical disperse F. Non mechanical disperse processingprocessing

Critical fluids liposome processCritical fluids liposome process Super critical or near critical fluids are gases CO2 and Super critical or near critical fluids are gases CO2 and

propane under ambient conditionspropane under ambient conditions When compressed at conditions above their critical When compressed at conditions above their critical

temperature and pressure, these substances become temperature and pressure, these substances become fluids with liquid like density and gas like properties of fluids with liquid like density and gas like properties of low viscosity and high diffusivity.low viscosity and high diffusivity.

The gaseous characteristics increase mass transfer rate, The gaseous characteristics increase mass transfer rate, thereby decrease processing timethereby decrease processing time

A circulating pump operating in a high pressure loop A circulating pump operating in a high pressure loop ensures good mixing between the supercritical fluids and ensures good mixing between the supercritical fluids and the liposomal raw materialsthe liposomal raw materials

After specified residence time, the resulting mixture is After specified residence time, the resulting mixture is trough the dip tube with its nozzle in a decompression trough the dip tube with its nozzle in a decompression chamber that contains aqueous solution or fine chamber that contains aqueous solution or fine dispersion of drug for liposomal encapsulation. dispersion of drug for liposomal encapsulation.

Fine suspension and size Fine suspension and size reduction equipmentreduction equipment

Three – roll millsThree – roll mills Ball mills or jar millsBall mills or jar mills Continuous stirred media millsContinuous stirred media mills

Three roll millsThree roll mills Capable of dispersing small tightly bound Capable of dispersing small tightly bound

agglomerates and hard discrete particlesagglomerates and hard discrete particles Premixed suspension allowed to travel Premixed suspension allowed to travel

between rotating rolls that are located between rotating rolls that are located about 10- 50 microns apart.about 10- 50 microns apart.

The particles not only subject to very high The particles not only subject to very high shear mechanical crushing and smearing shear mechanical crushing and smearing

Three rolls are named as feed roll, center Three rolls are named as feed roll, center roll and apron rollroll and apron roll

Three roll millsThree roll mills The shear rates in a three – roll mill The shear rates in a three – roll mill

are a function ofare a function of– The roll radius, R inchesThe roll radius, R inches– The difference in rpm of the rolls in The difference in rpm of the rolls in

contact, contact, δδ rpm rpm– Clearance between the rolls known as Clearance between the rolls known as

nip clearance, z (mils)nip clearance, z (mils) Shear rate, = 105R Shear rate, = 105R δδ /z /z

Ball millBall mill For true size reduction of fine particles For true size reduction of fine particles

or for deagglomeration of very tightly or for deagglomeration of very tightly bound agglomeratesbound agglomerates

Small version of ball mill is known as Small version of ball mill is known as jar mill jar mill

Disadvantage is time consuming Disadvantage is time consuming processprocess

For difficult to grind materials, ball mill For difficult to grind materials, ball mill is still the machine of choiceis still the machine of choice

Agitated bead millsAgitated bead mills Just like ball mill ,the bead mill uses a Just like ball mill ,the bead mill uses a

charge of inert small balls around 2-8mm in charge of inert small balls around 2-8mm in diameterdiameter

If the beads are ceramic – media millIf the beads are ceramic – media mill If the beads are steel balls- shot millIf the beads are steel balls- shot mill Large grains of sand(3mm)- sand millLarge grains of sand(3mm)- sand mill The cylinder is either horizontal or verticalThe cylinder is either horizontal or vertical Not often used in ph. industry, except when Not often used in ph. industry, except when

particle size requirements fall below 10 particle size requirements fall below 10 micronsmicrons

Problems encountered in dispersion system

Suspensions are unstable from the thermodynamic poin of view; however, they can be kinetically stable over a large period of time, which determines their shelf life. This time span needs to be measured to ensure the best product quality to the final consumer. “Dispersion stability refers to the ability of a dispersion to resist change in its properties over time.Migration phenomena: whereby the difference in density between the continuous and dispersed phase, leads to gravitational phase separation. In the case of suspensions sedimentation occurs as the dispersed phase is denser than the continuous phase.Particle size increase phenomena: whereby the suspended particles join together and increase in size. Below are the two types of this phenomena.

Technique monitoring physical stability

Multiple light scattering coupled with vertical scanning is the most widely used technique to monitor the dispersion state of a product, hence identifying and quantifying destabilisation phenomena.

It works on concentrated dispersions without dilution. When light is sent through the sample, it is backscattered by the particles. T

he backscattering intensity is directly proportional to the size and volume fraction of the dispersed phase. Therefore, local changes in concentration (sedimentation) and global changes in size (flocculation, aggregation) are detected and monitored.

Emulsion Emulsion InstabilityInstability There are three types of instability: flocculation, There are three types of instability: flocculation,

creaming, and coalescence. Flocculation creaming, and coalescence. Flocculation describes the process by which the dispersed describes the process by which the dispersed phase comes out of suspension in flakes. phase comes out of suspension in flakes. Coalescence is another form of instability, which Coalescence is another form of instability, which describes when small droplets combine to form describes when small droplets combine to form progressively larger ones. Emulsions can also progressively larger ones. Emulsions can also undergo creaming, the migration of one of the undergo creaming, the migration of one of the substances to the top (or the bottom, depending substances to the top (or the bottom, depending on the relative densities of the two phases) of on the relative densities of the two phases) of the emulsion under the influence of buoyancy or the emulsion under the influence of buoyancy or centripetal force when a centrifuge is used.centripetal force when a centrifuge is used.

Surface active substances (surfactants) can increase Surface active substances (surfactants) can increase the kinetic stability of emulsions greatly so that, the kinetic stability of emulsions greatly so that, once formed, the emulsion does not change once formed, the emulsion does not change significantly over years of storage. A Non-Ionic significantly over years of storage. A Non-Ionic surfactant solution can become self-contained under surfactant solution can become self-contained under the force of its own surface tension, remaining in the the force of its own surface tension, remaining in the shape of its previous container for some time after shape of its previous container for some time after the container is removed. Superfluids flow with zero the container is removed. Superfluids flow with zero friction and can escape their containers; an ionic friction and can escape their containers; an ionic solution tends to retain its current shape.solution tends to retain its current shape.

““Emulsion stability refers to the ability of an Emulsion stability refers to the ability of an emulsion to resist change in its properties over emulsion to resist change in its properties over time.” D.J. McClements.time.” D.J. McClements.

Technique monitoring physical Technique monitoring physical stabilitystability

Multiple light scattering coupled with vertical Multiple light scattering coupled with vertical scanning is the most widely used technique to scanning is the most widely used technique to monitor the dispersion state of a product, hence monitor the dispersion state of a product, hence identifying and quantifying destabilisation identifying and quantifying destabilisation phenomena.phenomena.

It works on concentrated emulsions without It works on concentrated emulsions without dilution. When light is sent through the sample, it dilution. When light is sent through the sample, it is backscattered by the droplets. The is backscattered by the droplets. The backscattering intensity is directly proportional to backscattering intensity is directly proportional to the size and volume fraction of the dispersed the size and volume fraction of the dispersed phase. Therefore, local changes in concentration phase. Therefore, local changes in concentration (Creaming) and global changes in size (Creaming) and global changes in size (flocculation, coalescence) are detected and (flocculation, coalescence) are detected and monitored.monitored.

Introduction to Colloidal Introduction to Colloidal systemssystems

DefinitionDefinition

Colloids are glue-like Colloids are glue-like substances, substances,

diffuse very slowly, and do diffuse very slowly, and do not dialysenot dialyse

suspensions> 1000 nm

Types of disperse systems (W. Ostwald)

Disperse systems

colloidal dispersions1 bis 1000 nm

solutions< 1 nm

DefinitionDefinitionAny particle that has Any particle that has

some linear dimension some linear dimension between 1 nm and between 1 nm and

1 1 μm is considered a μm is considered a colloid!colloid!

However, the limits are rather However, the limits are rather arbitrary.arbitrary.

• A state of subdivision in which the particles, droplets, or bubbles dispersed in another phase have at least one dimension between

1 – 1000 nm

• All combinations are possible between gas, liquid, and solid

W. Ostwald

Definition:

History of Colloid ChemistryHistory of Colloid Chemistry

1927 Burry, Ekwall: Associating 1927 Burry, Ekwall: Associating ColloidsColloids

1929 Staudinger: 1929 Staudinger: MacromoleculesMacromolecules

Associating ColloidsAssociating Colloids

Amphiphilic self-organizing Amphiphilic self-organizing systemssystems

Colloids are associated Colloids are associated physically, not chemicallyphysically, not chemically

Size and shape of the associates Size and shape of the associates can changecan change

Macromolecules as colloidal Macromolecules as colloidal systemssystems

Any macromolecule consisting of Any macromolecule consisting of

101033 up to 10 up to 1099 atoms atoms

Any dispersed macromolecular Any dispersed macromolecular coil having colloidal dimensionscoil having colloidal dimensions

History of Colloid ChemistryHistory of Colloid Chemistry

1923 Svedberg: 1923 Svedberg: UltracentrifugationUltracentrifugation

1932 Ruska: Electron Microscopy1932 Ruska: Electron Microscopy

The Colloidal DomainThe Colloidal Domain

One dimension between 1 and 1000 One dimension between 1 and 1000 nmnm

All combinations of dispersed matterAll combinations of dispersed matter

Classification: - colloidal dispersionsClassification: - colloidal dispersions

- associating colloids- associating colloids

- macromolecules- macromolecules

BiomineralizationBiomineralization

Inorganic Inorganic componentcomponent

Organic Organic componentcomponent

OrganismOrganism

SiOSiO22 ** x x HH22OO composite of composite of hydrocarbonhydrocarbon

and proteinand protein

DiatomeenDiatomeen

Aragonite, Aragonite, CaCOCaCO33

composite of composite of hydrocarbonhydrocarbon

and proteinand protein

Perl oysterPerl oyster

Hydroxyapatit, Hydroxyapatit, CaCa1010(PO(PO44))66(OH)(OH)22

composite of composite of collagenfilament collagenfilament

and proteinand protein

Bone and teethBone and teeth

Nanoparticles as Nanoparticles as QuantendotsQuantendots

Color effects in glases Color effects in glases

(e.g. CdS or gold)(e.g. CdS or gold) Non linear optical effects Non linear optical effects

(fast optoelectronical switches)(fast optoelectronical switches) High storage capacity High storage capacity

(optical storage)(optical storage)

Formation of NanoparticlesFormation of Nanoparticles(Nanotechnology)(Nanotechnology)

Particle formation from gas phasesParticle formation from gas phases

Particle formation from dropletsParticle formation from droplets

Particle formation from Sol-Gel-Particle formation from Sol-Gel-ProcessesProcesses

Nanoparticles produced by Nanoparticles produced by nucleation processesnucleation processes

Colloidal SulfurColloidal Sulfur

Colloidal GoldColloidal Gold

Latex ParticlesLatex Particles

NanocrystallitesNanocrystallites

Conditions for the production of Conditions for the production of monodisperse nanoparticlesmonodisperse nanoparticles

- Heterogeneous nucleation- Heterogeneous nucleation

- La Mer diagram- La Mer diagram

DisciplinesDisciplines and and TopicsTopics for which Colloids for which Colloids and colloidal phenomena are importantand colloidal phenomena are important

Analytical chemistryAnalytical chemistry Physical chemistryPhysical chemistry BiochemistryBiochemistry Material ScienceMaterial Science Petroleum SciencePetroleum Science Household productsHousehold products Imaging technologyImaging technology

Adsorption phenomena, Adsorption phenomena, chromatographychromatography

Nucleation, supersaturation, Nucleation, supersaturation, liquid crystalsliquid crystals

Electrophoresis, osmosis, Electrophoresis, osmosis, ultrafiltrationultrafiltration

Ceramics, fibres, powder Ceramics, fibres, powder metallurgymetallurgy

Oil recovery, Oil recovery, Milk, beer, cosmeticsMilk, beer, cosmetics Emulsions, printing inks, Emulsions, printing inks,

paper coatingpaper coating