Product Stability. John Woodruff. Creative Developments (Cosmetics) Ltd. or How to make sure your product stays as good as new

Transcription

1 Product Stability or How to make sure your product stays as good as new John Woodruff Creative Developments (Cosmetics) Ltd 1

2 Product Stability What is it? How do we test it? How can we improve it? 2

4 Definition of Stability In mathematics, stability theory addresses the stability of solutions of differential equations and of trajectories of dynamical systems under small perturbations of initial conditions. In probability theory, the stability of a random variable is the property that a linear combination of two independent copies of the variable has the same distribution, up to location and scale parameters.... 4

5 Definition of Stability - the quality of being enduring and free from change or variation - resistant to change of position or condition - firm and dependable; subject to little fluctuation - not taking part readily in chemical change 5

6 Definition of Stability What do we understand about it with regard to cosmetic products? That a product remain fit for purpose Appearance Purity including lack of microbial contamination Efficacy That it remains fit for purpose for a period of not less than 36 months from manufacture and not less than its PAO declaration 6

7 7 Examples of Instability

8 Examples of Instability Obvious Emulsion breakdown Perfume changes Colour changes Viscosity changes Fungal growth Wax crystallisation Sediment in clear lotions 8

9 Examples of Instability Less Obvious ph changes Loss of activity Vitamins Antioxidants Enzymes Preservatives Photo-degradation of UV filters Microbial growth 9

10 Emulsion Creaming 10

11 Emulsion Breakdown 4 days at room temperature 1 month at room temperature 1 month at 45 C 4 days at room temperature 1 month at room temperature 11 1 month at 45 C

12 Viscosity Changes Increasing Decreasing Stable Initial 5 days days 12

13 Worst Nightmare! Atmospheric Mould Colonies 13

14 Crystal Growth 14

16 Testing for Stability Prepare a pilot batch and store it in its retail packaging and check that it remains fit for purpose for a period of not less than 36 months from manufacture and not less than its PAO declaration! Impractical What other options? 16

17 Testing Schedules Examples of suitable schedules are given in the IFSCC Monograph Boots publishes a scheme that its suppliers are expected to use - GR10 Distance Learning Course (DLC) includes suggestions in its module on stability 17

18 Testing Schedules IFSCC Monograph 40 ambient humidity - retain as control 200 / 250 ambient humidity - 60 months 370 ambient humidity - 6 months 450 ambient humidity - 3 months 370 & 80% relative humidity - 1 month Freeze / Thaw Light exposure 18

19 Testing Schedules DLC Recommendations 19

20 DLC Recommendations 1 month assessment (all storage conditions) 2 month assessment (all storage conditions) 3 month assessment (all storage conditions) 6 month assessment (all storage conditions) 9 month assessment (all storage conditions) 1 year assessment (all storage conditions) 18 month assessment (5 C and RT storage conditions only) 2 year assessment (5 C and RT storage conditions only) 30 month assessment (5 C and RT only) 3 year assessment (5 C and RT storage conditions only). 20

21 Testing Schedules Boots recommendation - Stability and final pack compatibility of all cosmetic and toiletry products should be assessed to establish that they are stable and that no separation, crystallisation, contamination, degradation or other instability occurs within the claimed product shelf life Must be safe to use, effective and stable in final pack for at least 36 months at: Must be safe to use, effective and stable in final pack for at least 3 months at: Products sold in temperate climates 0 C to 23 C 30 C Products sold in tropical climates 0 C to 30 C 40 C Stability Requirements Product must also be safe to use within their specified Period After Opening (PAO), no matter at what point in their shelf life they are first opened. 21

22 What should be checked? 22

23 23

24 What is Important 24 Consider the function of the product under test and decide whether or not the changes observed could affect this Consider the safety of the product under test and decide whether or not the changes observed could affect this Consider whether the changes observed affect the aesthetics of the product under test Note under what storage conditions any changes observed take place and try to relate these to the environment in which the product is to be sold Look for significant trends in changes of product attributes

25 Talking Points What is important for this product in this packaging for this market? Setting product specification Minimum and maximum for each parameter Why these numbers? Have products been prepared and tested at extreme specification limits? Release specifications / shelf-life specifications What matters? 25

26 Accelerated Testing for Stability Prepare a pilot batch and store it in its retail packaging: 26 Room Temperature (RT) for 24 months 4 C for 3 months 40 C for 3 months 4 C/40 C Cycle for a number of cycles In a N-facing window or a light box for 3m

27 Testing for Stability Monitor for changes in appearance (Subjective measurements) Homogeneity Colour Glass slides Microscope Texture and skin feel Odour 27

28 Testing for Stability Monitor emulsion stability (Physical changes) Emulsion breakdown Creaming or settling 28 Glass slides aeration and density/opacity Microscope droplet size changes; crystals Viscosity changes Rheological changes Centrifuge tests Turbiscan Lumifuge

29 Emulsion Creaming 3 months at 40C 18 months at RT What ways are available for quicker results 29

30 Microscope Examination 4 days at room temperature 1 month at room temperature 4 days at room temperature 1 month at room temperature 30 1 month at 45 C 1 month at 45 C

31 Viscosity Changes These are actual viscosity graphs of 5 different w/o emulsions differing only in emulsifier used 31

32 Rheological Changes For suspensions measure yield values 32 Yield value is the minimum force necessary to induce flow Measured using a rheometer or a Brookfield Digital Viscometer with small sample adaptor Yield values may be used to determine the suspending power of a composition; very useful when developing scrubs

33 Accelerated Stability Testing Centrifuge Ultracentrifuge 33 5 minutes or more at 5,000 rpm A centrifuge designed to run at very high speeds and thus generate very high centrifugal force is called an ultracentrifuge. Suspensions which would settle only very slowly or not at all under gravity can be made to separate quickly in such a device!

34 The LUMiFuge Demixing phenomena, like sedimentation, flotation or consolidation are directly measured by the LUMiReader, LUMiFuge or LUMiSizer due to the patented cutting-edge STEP -Technology. This permits to obtain Space- and Time-resolved Extinction Profiles over the entire sample length of up to 12 different samples simultaneously. Parallel light (I0) illuminates the entire sample cell and the transmitted light I is detected by thousands of sensors arranged linearly across your whole sample from top to bottom with a microscale resolution. Transmission is converted into extinction by lg I/I0 and particle concentration may be calculated. 34

35 The LumiFuge The multisample analytical centrifuge LUMiFuge accelerates the demixing process up to 2300 times compared to traditional test tube tests. Stability tests and shelf-life determinations of original dispersions are up to 2500 times faster than performed in a test tube under earth gravity. 35

36 Turbiscan The Turbiscan measures transmitted and reflected light passing through a sample and graphs the results. Differences over time are due to changes in droplet size and distribution 36

37 Principle of Measurement Particle migration Sedimentation or creaming Particle size variation Coalescence or flocculation t=0 min t=0 min t=15 min t=15 min

38 Testing for Stability Monitor chemical changes ph Loss of activity Vitamins Antioxidants Enzymes Preservatives UV Filters 38 Photo-degradation of UV filters

39 Testing for Stability Monitor preservative efficacy Initial challenge test to accepted protocols Head space test CTFA, CTPA, B.P. and European Pharmacopoeias It is recommended that this be done if widemouthed container is used to assess risk of mould and fungal growth Challenge testing of stability samples It is recommended that this be done after 3 months stability testing at RT and 40C 39

40 Packaging Compatibility STRESS CRACKING - The Hedley Test Applied to detergent/oil based products which are contained in polythene, PVC, PET. 12 samples filled to the declared volume and closure fitted to the correct torque. Stored at 60 C for 48 hours, 6 upright and 6 inverted. At the end of the test no containers should show any signs of cracking. 40

41 Packaging Problems Panelling of polyethylene Dissolving of PVC Oils causing brittle polystyrene Corrosion of aluminium Discolouration of plastic Transpiration of perfume through plastic Absorption of actives by pack wall 41 Etc.

43 Emulsion Stability A two-phase system, consisting of two completely immiscible or partially miscible liquids, one being dispersed in the other in the form of very fine droplets Water-in-Oil = w/o Oil-in-Water = o/w Oil-in-Water-in-Silicone = o/w/si 43

44 Emulsion Stability What makes it stable? 44 Correct choice of emulsifier system Compatible ingredients Compatible ph Correct mixing method Compliance with specification Compatible packaging Understanding possible causes of instability

46 HLB System HLB Number = E + P 5 where E = molecular weight percent of ethylene oxide content P = molecular weight percent of polyol content In the equation above the value (E+P) can take on any value up to a maximum of 100. This means that the HLB number assigned to the emulsifier will lie within the range of 0 to

47 HLB System HLB number of surfactant and type of emulsion formed < 3 none 3 8 water-in-oil (W/O) 8 15 oil-in-water (O/W) > 15 solubilisation 47

48 Liquid Crystals Some emulsifier systems form liquid crystal structures, which contribute to stability Examples: Cetearyl glucoside with cetearyl alcohol Sorbitan olivate and cetearyl olivate Sorbitan stearate with sorbityl laurate Sorbitan stearate with sucrose cocoate Polyglyceryl-3 methylglucose distearate Potassium cetyl phosphate and hydrogenated palm glycerides Lauryl glucoside & polyglyceryl-2 dipolyhydroxystearate 48

49 Liquid Crystal Emulsion 49

50 Liquid Crystal Emulsion 50

51 Other Emulsifiers 51 Polymers e.g. Acrylates/C10-30 Alkyl Acrylate Crosspolymers Polyethylene glycol ethers (Oleth-10; Laureth-10 etc) Polysorbates with Sorbitan esters e.g. Polysorbate-20 with Sorbitan monolaurate Glyceryl esters e.g. Glyceryl cocoate / laurate etc. Alkolylated dimethicones (AKA Dimethicone copolyols) Soaps e.g. triethanolamine stearate; Potassium peanutate etc. PG Esters e.g. Propylene glycol myristate etc. Sucrose esters e.g. Sucrose laurate / myristate etc

53 Incompatible Ingredients Carbomers and salts Kathon CG contains a salt Dihydroxyacetone and formaldehyde Many preservatives are formaldehyde donors Enzymes and chelating agents EDTA and its salts Parabens Ethoxylated emulsifiers 53 etc. etc.

54 ph vs Viscosity Typical carbomer system Viscosity ph 5.0 ph 5.5 ph 6.0 ph 6.5 ph 7.0 ph 7.5 ph

55 Correct Mixing Methods Use laboratory mixing equipment which represents that available in the factory 55

56 Pilot Scale 56

57 Correct Mixing Methods 57

58 Compliance with Specification How was the specification set? Was stability tested on a product within the specification set? 58 One small laboratory batch? 2 or more laboratory batches with reproducible results? Pilot scale batch? Better still; were 2 or more batches at limits of specification tested

59 Emulsion Stability What causes instability? For an emulsion to become unstable the dispersed phase droplets must collide and coalesce Coalescence of two dispersed phase droplets produces a bigger dispersed phase droplet, and the ultimate outcome of this process is complete phase separation, indicating emulsion instability 59

60 Forces of Attraction F = -Aa 12H where F = London-Van der Waals force of attraction A = Hamaker constant a = radius of the dispersed phase droplets H = distance between two adjacent dispersed phase droplets 60

61 F = -Aa 12H Forces of Attraction Good stuff but what does it mean for emulsion stability From the equation it can be seen that the magnitude of the attractive force increases as the radius of the dispersed phase droplets becomes larger and less as the distance between them is increased Stability = Small droplets far apart 61

62 Stokes Law Stokes Law describes the factors influencing the velocity of a solid sphere, moving under the force of gravity, in a continuous liquid medium V = 2a2(ρc ρd)g 9μ 62 V = velocity of the dispersed phase droplet a = radius of the dispersed phase droplet ρd = density of the dispersed phase ρc = density of the continuous phase g = acceleration due to gravity μ = viscosity of the continuous phase

63 Stokes Law: Good stuff but what does it mean for emulsion stability V = 2a2(ρc ρd)g 9μ To improve stability reduce V 63 Reduce a - size of dispersed phase droplet Reduce (pc-pd) by matching density of the dispersed phase with that of the continuous phase g = acceleration due to gravity difficult to alter Increase μ - viscosity of the continuous phase

64 What droplet size? Emulsion appearance and approximate particle size 64 milky-white greater than 1μ blue-grey μ translucent μ transparent less than 0.05 μ

65 Emulsion Stability 65 Careful selection of emulsifiers Small droplet size (High shear mixing; PIT technology) Lamellar structures by using emulsifiers that form liquid crystals Match SG of oil phase to aqueous phase Adjust rheological properties by using carbomers or xanthan gum, starch or CMC derivatives etc.

66 Add Rheological Additive 0% UltraThix P % Cerasynt % UltraThix P % Cerasynt % UltraThix P % Cerasynt 945 Cerasynt 945 = Glyceryl stearate (&) laureth-23 Ultrathix P100 = Acrylic acid/vp Crosspolymer 66

67 Add Right Rheological Additive Zinc Oxide nano particles Carbomer 67 Acrylic acid/vp Crosspolymer

68 Microscope Examination Titanium Dioxide Nano particles Carbomer 68 Acrylic acid/vp Crosspolymer

69 Sun Protection Products These present special problems 69 Emulsion stability Agglomeration of micronised sunscreens Crystallising of organic sunscreens Failure to meet SPF declaration Failure to meet UVA requirements Failure to meet water resistance claims Photodegradation of actives

70 Sun Protection Products Agglomeration of micronised sunscreens can be seen under a microscope at 1000x magnification 70 Use rheology modifiers to stop migration of particles Veegum is good. Acrylic acid/vp Crosspolymer is recommended

71 Preventing Agglomeration TiO2 Nano particles Zinc Oxide nano particles Acrylic acid/vp Crosspolymer 71

72 Crystallising of Organic Sunscreens Check solubility in oil phase If using Phenylbenzimidazole Sulfonic Acid ph is critical 72

73 Photodegradation of BMDBM 73

74 Improve UV Absorber Stability The UVA filter BMDBM is not photostable and may lose 60% or more of its activity at 360nm when exposed to solar radiation. EHMC destabilises BMDBM / octocrylene mixtures Benzophenone-3 stabilises BMDBM weakly; octocrylene stabilises EHMC strongly but does not stabilise BMDBM and ethylhexyl methoxycrylene stabilises BMDBM strongly. There is a relationship between the rate of photo decay of BMDBM and the dielectric constant of the oil phase. As the dielectric constant increases BMDBM is progressively more stable until it reaches maximum stability at about 8.8, after which its rate of decay increases again 74

75 Sun Protection Products Failure to meet SPF declaration Failure to meet UVA requirements Don t put to much faith in SPF boosters Use the Ciba Sunscreen Simulator then in-vitro then in-vivo 75 Study the suppliers literature and many articles on the subject Make sure the formula complies with latest EU Recommendation (UVA =>1/3rd UVB)

76 Thank you for your time and may all your creations be stable John Woodruff 76