Emulsion technologyEmulsion technology

SCS Summer school July 13, 2013

Steve Boothroyd

Thinking about how you would develop any sort of product what are the key things you should consider during development?

My thoughts in no particular order of importance

Does your Consumer love it?Does it meet the Claims you want to make for it?Is it safe?Is it stable?Can you make it on a larger scale consistently?Can you afford it?

Does you consumer love it?

Why would you choose to use an emulsion instead of another technology?

Take a few minutes in your tables to come up with 5 possible answers

Does you consumer love it?

Possible answers…

•They feel good!•You can pack different actives in different phases•You have the option to change lots of things•They can take a range of formats•They are cost effective

What is an emulsion?

A dispersion of one or more immiscible liquid phases in another, the distribution being in the form of tiny droplets.

What is an emulsion?

A dispersion of one or more immiscible liquid phases in another, the distribution being in the form of tiny droplets.

Simple emulsion types

Water-in-oil

Water droplet(dispersed phase)

Oil(continuous phase)

Oil-in-water

Oil droplet(dispersed phase)

Water(continuous phase)

Emulsion orientation

• The phase that is added tends to become the internal phase

• The predominant solubility of the emulsifier tends to determine the external phase (Bancroft’s rule)

• Generally, the phase of the greatest volume tends to become the external phase

• The phase in which the stirrer is placed tends to become the external phase

Droplet size measurement

Laser Particle Analyser

Opticalmethod

Laser method

Use of sound waves (Malvern)

Audio method

Microscopy

• Uses • Droplet size and size distribution• Quality of manufacturing process e.g.

undispersed thickener• Detecting unwanted crystallisation • Early indications of instability e.g.

flocculation, coalescence, synerisis• Comparison of different emulsions• Liquid crystals

What does an emulsion look like?

What does an emulsion look like?

What does an emulsion look like?

What don’t you want to see?

Is it Stable?

What are the stability risks associated with emulsions?

Take a few minutes in your tables to come up with some possible answers

Is it Stable?

What are the stability risks associated with emulsions?

•Creaming•Sedimentation•Flocculation•Coalescence•Phase Inversion•Ostwald Ripening

Is it Stable?

Why is that?

•Emulsions are thermodynamically unstable•Their natural tendency is to revert to a state of least energy i.e. separated into two layers•The process of emulsification is to produce droplets but also to maintain them in this state over a reasonable shelf life

Creaming / Sedimentation

• No change in droplet size• Reversible• Driven by density difference• Usually results from gravitational forces

Creaming Sedimentation

Coalescence

• Not reversible• May lead from flocculation, creaming /

sedimentation or Brownian motion• Involves 2 drops coming together

• May lead to complete separation

Stokes’ Law

Defined as:-

Velocity of droplet (v) = (2a2 g (ρ1 – ρ2)) / 9η

Wherea = Radius of dispersed phase dropletρ1= Density of continuous (external) phaseρ2 = Density of continuous (internal) phaseg = Acceleration due to gravityη = viscosity of the continuous (external) phase

Van der Waals forces

Defined as

F = - Aa12H

Where

F = Van der Waals forces of attractionsA = Hamaker constanta = Radius of dispersed phase dropletsH = Distance between two adjacent dispersed

phase droplets

Is it Stable?

What can these two equations tell us that will help us make formulating decisions to improve stability?

Take a few minutes in your tables to come up with some possible answers

• From Stokes’ Law• Thicken the continuous phase. This increase η

and reduces the velocity• Reduce the particle size by greater or more

effective mixing.This has a major effect as a is squared

• Reduce the difference in specific gravity between the phases

• Additionally from Van der Waal• Increase the distance between droplets either

through thickening the water phase to reduce mobility, reducing particle size, or introducing materials that avoid droplets getting too close e.g. polymers

Improving emulsion stability

• Charge stabilisation• Interfacial film strengthening

• with powders

• with polymers

• With non-ionic emulsifiers• Steric stabilisation• Continuous phase viscosity• Droplet size• Co-emulsifiers / polar waxes• Liquid crystals

Improving emulsion stability

Charge stabilisation

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Negatively charged oil droplets repel each other

Stability affected by quantity of electrolyte and whether M+ or M++

Improving emulsion stability

• Interfacial film strengthening• Reduces the probability of coalescence

when droplets collide

Interfacial film strengthening with powders

Powder particle size must be very small

Powder must have an affinity for both the oil and water phase

Improving emulsion stability

Interfacial film strengthening with polymers

Polymer sits at emulsion interface

Polar groups orient into the water phase

e.g. Cetyl PEG/PPG-10/1 Dimethicone Acrylates/vinyl isodecanoate crosspolymer

Improving emulsion stability

Interfacial film strengthening with non-ionic emulsifiers

Oil

Tighter packingat interface

Interface strengthening is dependent on the number of molecules that are packed into the interface

Improving emulsion stability

• Polymer molecules adsorb on the surface of oil droplets, leaving tails and loops extending into the water phase

• Polymer molecules must be strongly adsorbed at interface

• There must be high coverage of droplet surface with polymer

• The 'tails and loops' must be soluble in the water phase

• e.g. Cetyl PEG/PPG-10/1 Dimethicone

Improving emulsion stabilitySteric stabilisation

• Continuous phase viscosity• Thickening the water phase restricts

movement of oil droplets• Thickeners with yield points are most

effective

• Droplet size

Increasing stability

Improving emulsion stability

• Co-emulsifiers / polar waxes• e.g. Cetyl alcohol

• Co-emulsifiers have weaker surface activity than primary emulsifiers

• Adds body and helps prevent coalescence

Improving emulsion stability

Is it Safe?

What are the key components of an emulsion that contribute to safety risk?

Is it Safe?

What are the key components of an emulsion that contribute to safety risk? Here are some possibilities

•Preservatives•Fragrance•Actives•Emulsifiers

What is an emulsifier?

Water lovinghead

Oil lovingtail

'Hydrophilic''Lipophobic'

'Lipophilic''Hydrophobic'

Potential irritation

• Emulsifiers, since they are surface active, may be a factor in increasing the risk of irritation

therefore

• Excessive levels of emulsifier should be avoided

• The most appropriate type of emulsfier should be chosen

Types of emulsifiers

• Anionics

The emulsifier carries a negative charge e.g. Sodium Stearate soap

C H COO Na3517

- +

Types of emulsifiers

Pros and Cons

• Were very common• Old fashioned• Not as versatile• Cheap• Limitations for actives due to high pH• Give negative charge to the oil droplet

Types of emulsifiers

• Cationic

The emulsifier carries a positive charge e.g. Palmitamidopropyl Trimonium Chloride

_ClCH3(CH2)14C NH(CH2)3

O

CH3

CH3

N CH3+

Types of emulsifiers

Pros and Cons

• Usage is not high in Skincare • Good barrier• Excellent silky skin feel• Give positive charge to oil droplet• Can be used at lower pH

Types of emulsifiers

• Non-ionic

Emulsifier carries no overall charge and can be made to form both Water-in-oil or Oil-in-water emulsifiers e.g. Steareth-2

CH3 (CH2 )16 CH2 (OCH2 CH2)2 OH

Types of emulsifiers

• Most common• Wide range• Versatile• Strengthen the emulsion interface• HLB system to predict choice

HLB system

0 10 20

LipophilicOil lovingNon polarOil soluble

HydrophilicWater lovingPolarWater soluble

HLB system

Emulsifier HLB 5

Emulsifier HLB 10

Emulsifier HLB 15Oilphase

Waterphase

Determining HLB values

Source: Croda ( Taken from Croda’s time saving guide to emulsifier selection” - training course available from Croda PLC)

How can you tell the difference?

• Measure conductivity – conductivity is higher with an O/W emulsion than a W/O emulsion

• Dye uptake - a water soluble dye will be taken up by an O/W emulsion

• Dispersion – an O/W emulsion will easily disperse in water

Required HLB for oil-in-water emulsion

Benzophenone-3Mineral oil Caprylic/Capric triglycerideCetyl alcoholVitamin E

710 - 11 515 - 16 6

HLB system

Required HLB for water-in-oil emulsion

Mineral oil 4

• Oil phase components can be given required HLB values

• Required HLB and emulsifier HLB are matched up

• Each oil will have 2 required HLB’s, one for oil-in-water emulsions, the other for water-in-oil emulsions

• The required HLB is published for some oils

Emulsifier selection using HLB

HLB Summary

• Pros– Empirical system

giving starting position

– Can be assessed practically

• Cons– Not good for anionics and

cationics– Need to know HLB of oil

which can vary– Can be time consuming

working out or measuring– Does not determine the

amount of emulsifier needed

Emulsifier blends

In the HLB system the HLB of the emulsifier blend is additive for example if an oil system had a required HLB of 10 you could use either

EmulsifierHLB 10

EmulsifierHLB 5

EmulsifierHLB 15or

Emulsifier blendsFor a given blend of non-ionic emulsifiers, where Emulsifier A is more lipophilic than Emulsifier B

Emulsifier A Emulsifier B

Oil Oil Tighter packingat interface

Considerations when choosing an emulsifier

• Type of emulsion• Oils to be emulsified• Processing - hot or cold• Effect on skin• Properties of the emulsion• Cost• Level of electrolyte

Can you make it on a larger scale consistently?

What are the differences that would impact on the manufacture of an emulsion between lab and factory?

Take a few minutes in your tables to come up with some possible answers

Can you make it on a larger scale consistently?

What are the differences that would impact on the manufacture of an emulsion between lab and factory?

Heating/ Cooling ratesStirring/ Shear rates

How are emulsions formed?• In order to overcome the barrier between the oil

and water we need to add energy• This is derived from two sources:-

• For long term stability both forms are needed

Chemical energy + Mechanical energy (emulsifier) (homogeniser)

Two key requirements for creating a stable emulsion

• Apply enough energy to the two phases to create a dispersion

• Stabilise the created dispersion

• Maintain a small droplet size• Increase the external phase viscosity to

reduce movement• Reduce phase density difference

Two stages of creating an emulsion

• Stage 1 – apply energy to the two phases to create a dispersion

• Generally heat to 70 - 75°C

• Stage 2 – stabilise the created dispersion• Maintain the small droplet size• Increase the external phase viscosity• Reduce phase density difference

Emulsion manufacture• Heating to this temperature can change the

level of the oil phase e.g. Cyclomethicone• If you need to add sensitive ingredients hot e.g.

sunscreens, then do it just prior to emulsification

• Avoid post emulsification addition of preservatives etc that partition between oil and water

Emulsion manufacture• After cooling the remaining ingredients are

added e.g. heat sensitive preservatives, perfumes.

• For W/O emulsions if you have to add preservatives these MUST be added prior to emulsification

• Only Oil-in-water emulsions can be made to weight easily

• BUT you must start thinking about scale up from the first formulation attempt

Emulsion manufacture• Laboratory

– Oil phase added with Silverson mixing

– Beaker placed in bowl of cold water and stir cooled

Takes approx 30 min

• Factory– Oil phase added with gate stirring followed by homogeniser mixingSize and distance

– Cold water passed through water jacket with gate stirring

Can take hours!

Emulsion manufacture

Phase Inversion Temperature(PIT)

• Occurs in some non-ionic emulsifier systems

• Linked to solubility of emulsifier in the respective phases • At different temperatures• In the presence of electrolyte

• Mostly used to transition water in oil to oil in water at a given temperature to produce desired small particle size

Phase Inversion Temperature(PIT)

• Unique for any given emulsifier or blend of emulsifiers

• Useful for explaining behaviour of emulsion systems

• Helps to understand formation of differing types of emulsion observed for a given blend of emulsifiers

Phase Inversion Temperature• Within the marked band a complex three phase mixture

is found• Above TU a W/O emulsion exists, below TL O/W• This temperature and band will be different for different

systems

0o

75o

0 20% emulsifier blend

Tem

per

atur

e oC TU

T

TL

2 phase

1 phase

2 phase

3 phase

Source: Kahlweit M: Microemulsions, Science 29 April 1998, p671-621

Phase Inversion Temperature• Why might this be the case?

• Solubility of ethoxylated emulsifiers increases with increasing ethoxylation

8 20

Sol

ubil

ity

Number of ethoxylate groups

Phase Inversion Temperature• Bancroft’s rule suggests that the emulsion formed

will depend on where the emulsifier is most soluble

• Oil in water where most water soluble

(hydrophilic)

• Water in Oil where most lipid soluble (lipophilic)

• Consequently changes the effective HLB

observed

• By correct choice of emulsifier conversion from a W/O to an O/W is possible