Emulsion technology SCS Summer school July 13, 2013 Steve Boothroyd 1

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 Oil-in-water Water-in-oil Water Oil droplet (dispersed phase) Water (continuous phase) Water-in-oil Water droplet (dispersed phase) Oil (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 method Laser Particle Analyser Audio method Use of sound waves (Malvern) Optical 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

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Coalescence Not reversible May lead from flocculation, creaming / sedimentation or Brownian motion Involves 2 drops coming together May lead to complete separation 21

Stokes’ Law Defined as:- Velocity of droplet (v) = (2a2 g (ρ1 – ρ2)) / 9η Where a = Radius of dispersed phase droplet ρ1= Density of continuous (external) phase ρ2 = Density of continuous (internal) phase g = Acceleration due to gravity η = viscosity of the continuous (external) phase 22

Van der Waals forces 12H Defined as F = - Aa Where F = Van der Waals forces of attractions A = Hamaker constant a = Radius of dispersed phase droplets H = Distance between two adjacent dispersed phase droplets 23

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

Thicken the continuous phase. This increase η and reduces the velocity 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 25 25

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 26

Improving emulsion stability Charge stabilisation - + 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 28

Improving emulsion stability Interfacial film strengthening with powders Powder particle size must be very small Powder must have an affinity for both the oil and water phase 29

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 30

Improving emulsion stability Interfacial film strengthening with non-ionic emulsifiers Oil Tighter packing at interface Interface strengthening is dependent on the number of molecules that are packed into the interface

Improving emulsion stability Steric stabilisation 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 32

Improving emulsion stability 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 34

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 loving head Oil loving tail 'Hydrophilic' 'Lipophobic' 'Lipophilic' 'Hydrophobic'

Potential irritation therefore 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 Na 35 17 - +

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 _ Cl CH3(CH2)14C NH(CH2)3 O CH3 N +

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 10 20 Hydrophilic Lipophilic Water loving Oil loving Polar 10 20 Lipophilic Oil loving Non polar Oil soluble Hydrophilic Water loving Polar Water soluble

HLB system Water Emulsifier HLB 5 Emulsifier HLB 10 Oil phase Water

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

HLB system Required HLB for oil-in-water emulsion Benzophenone-3 Mineral oil Caprylic/Capric triglyceride Cetyl alcohol Vitamin E 7 10 - 11 5 15 - 16 6 Required HLB for water-in-oil emulsion Mineral oil 4

Emulsifier selection using HLB 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

HLB Summary Pros Cons Not good for anionics and cationics 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 Emulsifier HLB 10 HLB 5 HLB 15 or

Emulsifier blends For a given blend of non-ionic emulsifiers, where Emulsifier A is more lipophilic than Emulsifier B Emulsifier A Emulsifier B Oil Oil Tighter packing at 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 rates Stirring/ Shear rates

Chemical energy + Mechanical energy 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 59

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 60

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 61

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 mixing Size and distance Cold water passed through water jacket with gate stirring Can take hours! 62

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 20 % emulsifier blend Temperature oC TU T TL 2 phase 1 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 Solubility 8 20 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