SUNSCREENS

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SUNSCREENS Karl A. Harris KAH Specialty
Products, LLC
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Why Sunscreens

• During the past ten years the number of cases of
  melanoma has increased more rapidly than that of
  any other form of cancer.
• More than 51,000 new cases are reported to the
  American Cancer Society each year.
• Baby Boomers
• Medications
• Ozone Layer

Skin Cancer Foundation, NY
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Sunscreen Market

• Sunscreen Market 2005, 1.1 Billion
• 820 Million Protection.
• 313 Million Self tanners.
• 22.5 Million After Sun.
• Sunscreen Market 2010, 1.25 Billion.

Source Information resources Inc., Excludes
Wal-Mart sales.
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Sunscreen Market
Leading Companies Ranked by s Dec. 2005

• Schering Plough 131 Million.
• Playtex 93 Million.
• Neutrogena 80 Million.
• Tanning Research 44 Million.
• Private Label 38 Million.
• LOreal 23 Million.
• Solar 9 Million.
• Chattem 8 Million.
• European Tanning 5 Million.
• Sun Skin Care Research 4 Million.

Source Information resources Inc., Excludes
Wal-Mart sales.
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Sunscreen Market
Leading Brands Ranked by s Dec. 2005

• Banana Boat 64 Million.
• Coppertone 44 Million.
• Private Label 38 Million.
• Coppertone Sport 35 Million.
• Hawaiian Tropic 33 Million.
• Neutrogena 33 Million.
• Coppertone Water Babies 16 Million.
• Coppertone Endless Summer 14 Million.
• LOreal 13 Million.
• Banana Boat Sport 13 Million.

Source Information resources Inc., Excludes
Wal-Mart sales.
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Sunscreen Definitions
A substance, often in the form of a cream or
lotion, used to protect the skin from the
damaging ultraviolet rays of the sun. (The
American Heritage Second College Edition) A
substance or compound that absorb, reflex or
scatter the ultraviolet rays of the sun.(Karl
A. Harris)
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Ultraviolet Radiation
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Types of Solar Radiation

• UVAI (340-400nm)
• Can cause tanning but has minimal erythemal
  effect. Can cause long-term damage. Penetrates
  deeply.
• UVAII (320-340nm)
• Slight erythemal contribution
• UVB (290-320nm)
• Causes sunburn and is a major contributor to skin
  cancer development.
• UVC (200-290nm)
• Very energetic radiation. Absorbed by the Ozone
  layer.

K.Klein, Cosmetech Laboratories Inc.
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Ultraviolet Penetration
400
300
350
250
200
Stratum Corneum
EpiDermis
Dermis
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Time of Day Effect on UV-B
100
90
80
70
60
50
40
30
20
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Sunlight Distribution
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Sunscreens as Drugs
Articles intended for use in the
diagnosis, cure, mitigation, treatment or
prevention of disease Drug Names Articles
intended to affect the structure or any function
of the body ARE DRUGS.....
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Sunscreen Monograph
Final monograph establishes conditions under
which over-the counter (OTC) sunscreen drug
products are recognized as safe and effective and
not misbranded
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Sunscreen Monograph

• Proposed Monograph 1978
• Tentative Final Monograph 1993
• Final Monograph 1999 (May 21,1999)

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Sunscreen Monograph
FDA Category 1Sunscreen Active Ingredients
Octisalate 5 Oxybenzone 6 Padimate O
8 Enzulisole 4 Sulisobenzone 10 Titanium
dioxide 25 Trolamine salicylate 12 Zinc Oxide
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Aminobenzoic Acid (PABA)15 Avobenzone
3 Cinoxate 3 Dioxybenzone 3 Homosalate
15 Meridamate 5 Octocrylene 10 Octinoxate 7.5
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Sunscreen Monograph
Global Sunscreen Active Ingredients
Avobenzone 3 Homosalate 15 Octocrylene
10 Octinoxate 7.5 Octisalate 5
Oxybenzone 6 Enzulisole 4 Sulisobenzone
10 Titanium dioxide 25 Zinc Oxide 25
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Sunscreen Monograph

• SPF 30 Maximum
• Water Resistant
• 40 minute immersion
• Very Water Resistant
• 80 minute immersion
• PABA Free
• aminobenzoic acid (PABA)-free
• One year to comply

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Sunscreen Monograph

• Maximum Concentrations
• Minimum SPF of 2 in Combination Products
• Two years to Comply
• Sunblock Prohibited
• Sunscreen Products
• Drug or cosmetic, will be held to the same
  standard

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Sunscreen Monograph

• Statement of Intent
• Hair and nails contains sunscreen to protect
  product color
• Warning Labels
• Self tanners, This product does not contain a
  sunscreenand does not protect against sunburn

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Sunscreen Monograph

• Sunscreen Claims
• protects against skin aging, wrinkling and
  premature aging (unsupported)
• UVA Monograph
• FDA addresses at a later date
• Use TFM for UVA issues
• Foreign Marketing Data
• FDA addresses at a later date

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Sunscreen Monograph

• Sunscreen Claims
• All day protection and specific number of hours
  of protection (unsupported)
• Sunscreen Claims
• Shield from, protects from, filters or screens
  out the suns rays, suns harsh rays, or suns
  harmful rays, help prevent skin damage
  (unsupported)

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Sunscreen Monograph

• SPF Test
• Diffey method retained in final monograph
• Human testing (MED)
• PCDs
• Minimal sunburn protection (SPF 2-12)
• Moderate sunburn protection (SPF 12-30)
• High sunburn protection (SPF 30 or above)

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Sunscreen Monograph

• USP USAN
• All Category I sunscreens must comply with USP
  monograph
• No expiration dating
• Sunscreen Ingredients
• Only ingredients included in sunscreen monograph
  that have U.S. Pharmacopoeia monograph
• ZnO TiO2
• Non-chemical or chemical free (unapproved)

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Sunscreen Monograph

• Sunscreen Combinations
• Finished product must have a SPF of not less than
  the number of sunscreen active ingredients used
  inthe combination multiplied by 2
• Use Labeling (two bulleted statements)
• Helps prevent sunburn and
• Higher SPF gives more sunburn protection

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What is SPF

• The Sun Protection Factor SPF is the result of a
  biological procedure for measuring the
  effectiveness of UV protection products on human
  subjects against erythema.
• It was first devised in the 1950s by Schulze and
  has undergone a number of refinements to result
  in the test which is known today.
• It is a laboratory test which does not
  accurately represent how the users of finished
  products actually apply the product but it is the
  best which is available.

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SPF

• Sun Protection Factor
• MED (ps)/MED(us)
• UVB Absorbed (Sayre)
• ((SPF-1)/SPF))100
• SPF 2 absorbs 50
• SPF 15 absorbs 93.3
• SPF 30 absorbs 96.7
• SPF 50 absorbs 98

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Protection Calculation of UV-B Blocked
98
97.5
95
90
80
5
10
20
40
50
SPF
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M.E.D

• MED ... Minimal Erythema Dose
• "The smallest dose of UV radiation (expressed as
• joules per meter squared) that produces redness
• reaching the borders of the exposure site
• SPF ... Sun Protection Factor
• SPF value

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What is M.E.D

• Minimal Erythemal Dose.
• The M E D is the minimum dose of UV radiation
  required to show the first signs of burning, or
  reddening of the skin.

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Ultraviolet Transmittance Analyzers(In vitro)

• Labsphere
• Optometrics SPF-290

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How Sunscreen Chemicals Work
Absorbs High Energy UV Rays
Emits lower energy radiation (IR, Fluorescence,
cis - trans Isomerization) and energy transfer
(triplet state)
Chemical in excited state
N. Shaath
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General Structure of Most Sunscreens
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Product Range
The Neo Heliopan product range contains a
comprehensive selection of UV absorbers that play
an important role world-wide. This versatility
affords the formulator a high degree of
flexibility in developing suncare and cosmetic
products for daily use.
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Product Range
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Neo Heliopan AV and E 1000
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Neo Heliopan AV and E 1000
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Neo Heliopan AV and E 1000
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Neo Heliopan AV and E 1000
Important properties

• Broadly used as essential UV-B absorbers
• Excellent UV-B absorbers for UV-broadband
  protection products
• Excellent UV-B absorbers for waterproof products
• Very good compatibility to the skin
  comprehensive safety studies
• Moderate photostability
• Easily to incorporate into emulsions cold
  processing possible
• Excellent compatibility with cosmetic ingredients
• Excellent solvent for crystalline and oil-soluble
  UV absorbers E 1000 has a higher solvent
  capacity than AV

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Neo Heliopan Hydro
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Neo Heliopan Hydro
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Neo Heliopan Hydro
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Neo Heliopan Hydro
Solubility of Hydro (calculated as free acid) -
when neutralized with Triethanolamine approx.
56 g Hydro in 100 g of water - when neutralized
with Sodium Hydroxide approx. 33 g Hydro in 100
g of water - when neutralized with Potassium
Hydroxide approx. 6 g Hydro in 100 g of
water Equivalence points of the neutralization
curves when neutralized with -
Triethanolamine pH value 6.0 -
Monoethanolamine pH value 6.9 - Sodium
Hydroxide pH value 7.9 - Tetrahydroxypropyl
Ethylenediamine pH value 6.1 Recommended pH
value in finished products 7.0 to 7.5
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Neo Heliopan Hydro
Important properties

• Hydro is one of the most effective UV-B absorbers
• A tremendous SPF increase could be reached by
  combining Hydro with AV or E 1000 in sunscreen
  products. Only a minimum of concentration of
  these combinations is necessary to achieve the
  desired SPF
• Hydro is very suitable for water-based
  transparent sunscreen gels
• It is possible to formulate waterproof sunscreen
  products with Hydro
• Excellent photostability

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Neo Heliopan 303
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Neo Heliopan 303
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Neo Heliopan 303

• Main application
• Used in combination with other UV-B absorbers
  to formulate high SPF sunscreen products.
• Can improve the in-vitro photostability of
  Butyl Methoxydibenzoylmethane (patent
  situation has to be considered, e.g. L'Oréal).
• Advantages
• Excellent UV-B absorber to formulate waterproof
  sunscreen products because of its very high
  resistance to water wash-off.
• Shows remarkable protection in the shorter UV-A
  range (320 to 340 nm).
• Is excellent photostable.
• Easily to incorporate into emulsions.
• Cold processing of sunscreen products possible.
• Excellent solvent for crystalline and
  oil-soluble UV absorbers and cosmetic
  ingredients.

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Neo Heliopan OS HMS
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Neo Heliopan OS HMS
HMS
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Neo Heliopan OS HMS
Main application Co-UV-B absorber in sun block
products. OS HMS act in these products as a
very good solvent for the crystalline UV
absorbers like MBC and BB and increases the SPF.
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Neo Heliopan BB
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Neo Heliopan BB
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Neo Heliopan BB
Main application Co-absorber broadband
protection USA Combination with Octyl
Methoxycinnamate to achieve higher
SPF's Europe Combinations with AV or E 1000 to
achieve broadband protection
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NEO HELIOPAN 357- Introduction
Keto-Enol Form (UVA) Diketo Form
(UVC/UVB) 1-(4-Methoxyphenyl)-3-(4-t.butylphenyl
) propane-1,3-dione. Neo Heliopan 357 INCI
Name Butyl Methoxydibenzoylmethane USAN
Avobenzone A White to Pale Yellow Powder with a
Slight to Neutral Odour. Oil Soluble UVA Filter.
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NEO HELIOPAN 357- Introduction
Absorbance of Neo Heliopan 357 in EtOH (10mg/l).
Absorbance
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NEO HELIOPAN 357- Introduction - Legislation

• One of the Few UV Filters Registered Worldwide
• European Cosmetics Directive Annexe VII Part 1
  Max. Conc. 5.
• USA Final Monograph for OTC Sunscreens. Max.
  Conc. when Used Alone of 3.0. When Used in
  Combination With Other UV Filters it can ONLY be
  Used Together with Allowed Cinnamates (OMC,
  Cinoxate)
• Salicylates (OS, HMS, TEA Salicylate)
• Benzophenones (3, 4, Dioxybenzone)
• and Octocrylene up to a Max. Conc. Of 3.0.
• It Cannot be Used in Combination with Zinc
  Oxide, Titanium Dioxide, PBSA, Padimate O,
  Menthyl Anthranilate.
• Japan Up to 10 Depending Upon the Product
  Category.

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Butyl Methoxydibenzoylmethane is not very
photostable and substantial losses (gt 70) will
occur unless it is protected. The loss is both
Dosage and Formulation dependent. However there
are several possibilities. So what happens ???

• When exposed to UV Radiation 2 types of
  Photo-instability have been observed.

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The Mechanism of Action
BMDM may tautomerise from the UVA absorbing
keto-enol form (the most thermodynamically
stable) to the diketo form which does not absorb
in the UVA. The diketo tautomer thermally
reverts back to the keto-enol tautomer
TAUTOMER one of two or more structural isomers
that existin equilibrium and are readily
converted from one isomeric form to another. The
Columbia Encyclopedia, Sixth Edition. 2001.
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1. BMDM may fragment to non-UVA absorbing species

.
.

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2. BMDM may react with other molecules
Ethylhexyl Methoxycinnamate (EHMC / OMC)
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• Energy Transfer
• Under the right conditions, the excited molecule
  (in its triplet state) may return to the ground
  (singlet) state by transferring its energy to
  another molecule
• The excited molecule becomes a donor (D) the
  second molecule becomes an acceptor(A) DA
  ----gt DA
• A quenches D A is a triplet quencher

Note - The D (donor) is the excited state.
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• Triplet Quenching.
• It is possible to substantially increase the
  photostability of Butyl Methoxydibenzoylmethane
  by adding suitable triplet quenchers to the
  formulation.
• This is the reason why the UVB filters
  Methylbenzylidene Camphor and Octocrylene are
  effective Photostabilizers of Butyl
  Methoxydibenzoylmethane.
• However the use of Octocrylene is restricted by
  patents and the use of MBC by the lack of
  world-wide registration (USA, Japan).

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• Patent Restrictions
• Photostability of Butyl Methoxydibenzoylmeth
  ane

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• The combination of Octocrylene with BMDM is
  restricted by two families of patents

• 1. LOreal Patents

• 2. Roche (Givaudan) Patents

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• 1. LOreal Patents
• The Patents owned by LOreal include - EP 0 514
  491 B1 (US 5 587 150, AU 652 742 B2, CA 2076003,
  JP-B2 2 975 682, ZA 9101104)
• These claim the combination of 1 to 5 of BMDM
  with at least 1.0 of Octocrylene whereas the
  molar ratio of Octocrylene to BMDM is at least
  0.8 ( weight ratio of 0.95).
• The following are examples of the minimum
  concentrations of combinations of OCT BMDM that
  fall within the patent
• 1.0 BMDM 0.95 OCT 1.5 BMDM 1.43 OCT
• 2.0 BMDM 1.90 OCT 2.5 BMDM 2.38 OCT
• 3.0 BMDM 2.85 OCT

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• 2. Roche (Givaudan) Patents
• The Patents owned by Roche include EP 780 119 A1
  (US 6 033 649, AU 719 298 B2, JP 917 5974 A2.)
• They claim the combination of 0.1 to 5 of BMDM
  with at least 0.5 of Octocrylene whereas the
  molar ratio of Octocrylene to BMDM is less than
  0.8 ( weight ratio of 0.95).
• The following are examples of the maximum
  concentration which fall within the patent
• 1.0 BMDM 0.90 OCT 1.5 BMDM 1.35 OCT
• 2.0 BMDM 1.80 OCT 2.5 BMDM 2.25 OCT
• 3.0 BMDM 2.70 OCT

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• The Patents covering the use of MBC to
  Photostabilize BMDM have been neutralised due
  to the specified dosages of the patent gt 4.
  
• The current EU regulations now specify the
  maximum dosage of MBC is 4.

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Corapan TQ (previously known as Hallbrite
TQ) Product Number - 182585 Diethylhexyl
2,6-naphthalate C28 H40 O4 M.Wt. 440 ET
57-60 kcal/mol (Estimated from Phosphorescence
Spectra)
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• Corapan TQ
• Is a clear, practically odourless, very pale
  yellow liquid.
• Has a high refractive index _at_ 25C of 1.5250
  (can improve the appearance of the emulsion by
  adding gloss).
• Has a specific gravity _at_ 25C of 1.0202.
• Has an acid value of lt 1.0
• A purity (GLC) of 97 minimum.
• Is miscible in many cosmetic oils (including
  cyclomethicone (DC 345) gt20), but is immiscible
  in glycerin and water.
• Has a required HLB of 10-12.

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• Energy Transfer
• Under the right conditions, the excited molecule
  (in its triplet state) may return to the ground
  (singlet) state by transferring its energy to
  another molecule
• The excited molecule becomes a donor (D) the
  second molecule becomes an acceptor(A) DA
  ----gt DA
• A quenches D A is a triplet quencher

Note - The D (donor) is the excited state.
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• Corapan TQ is an excellent solvent for solid UV
  filters
• Butyl Methoxydibenzoylmethane 18
• Oxybenzone 17
• Octyl Triazone gt10
• Methylbenzylidene Camphor 20
• Diethylhexyl Butamido Triazone 15

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UV-B UV-A
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• Study 1. - Experiment demonstrating
  photostabilizing effect of Corapan TQ on BMDM
• Formulations containing
  1 BMDM prepared with
  0, 2, 4
  Corapan TQ
• Slides prepared on Vitro-skin
• Scans made before/after 10 MED exposure
• Absorbance curves are averages of 4 measurements

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UV-B UV-A
68 Loss _at_ 360nm
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Photostability of 1 BMDM O/W Formulation with
2 Corapan TQ
16 Loss _at_ 357nm
UV-B UV-A
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Photostability of 1 BMDM O/W Formulation with
4 Corapan TQ
7 Loss _at_ 357nm
UV-B UV-A
Formulations
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• Study 3. - Influence of Photostability of BMDM
  on in-vivo SPF and an illustration of how this
  can be used to generate high
  SPF formulations.

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UV-B UV-A
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UV-B UV-A
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3 BMDM 4 Corapan TQ in an O/W
Emulsion in-vivo SPF 12 (FDA Method).
UV-B UV-A
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3 BMDM 5 Octyl Salicylate 4 Corapan TQ in
an O/W Emulsion in-vivo SPF 17 (FDA Method).
UV-B UV-A
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3 BMDM 5 Octyl Salicylate 3 Oxybenzone
5 Corapan TQ in an O/W Emulsion, in-vivo SPF 32
(FDA Method).
UV-B UV-A
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Summary of Photostability of BMDM on in-vivo SPF
3 BMDM 3 BMDM 3 BMDM
3 BMDM 4 Corapan TQ 4 Corapan TQ 4
Corapan TQ 5 Octyl Salicylate 5 Octyl
Salicylate 3 Oxybenzone
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• Study 4. - The Influence of
  Ethylhexyl Methoxycinnamate (EHMC) on the
  Performance of Corapan TQ as a Photostabilizer
  of BMDM via
• Modified Colipa Method.
• SPF Determination (indicative result - 5
  subjects).

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Formulations prepared containing 0.75 BMDM and
1 EHMC
Absorbance Curve of Ethanol Solution of the
Emulsion Before After Irradiation
35 Loss _at_ 306 nm
40 Loss _at_ 357nm
87
Formulations prepared containing 0.75 BMDM and
1 EHMC with the addition of 2 Corapan TQ
Absorbance Curve of Ethanol Solution of the
Emulsion Before After Irradiation
26 Loss _at_ both 306 357nm
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Formulations prepared containing 0.75 BMDM and
1 EHMC, 2 Corapan TQ with the addition of
0.5 PBSA
Absorbance Curve of Ethanol Solution of the
Emulsion Before After Irradiation
20 Loss _at_ 357nm
15 Loss _at_ 306 nm
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• Study 4.1. - Conclusion.

• The data shows that Corapan TQ has a limited
  effect upon the photostability of BMDM when EHMC
  is present.

• The addition of a second UVB filter, PBSA,
  further protects EHMC and to a limited extent
  BMDM.

• The study indicates that Corapan TQ has an
  effect on the SPF result. The synergies from
  addition of a second UVB Filter further increases
  the SPF.

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• Study 4.2.
• O/W emulsions prepared containing
  2.0 BMDM,
  5.0 Ethylhexyl Salicylate, 15
  Homosalate, 6 Oxybenzone, from
  0 - 7.5 EHMC and
  from 0 - 6
  Corapan TQ .
• 0, 10 15 MED exposures.
• HPLC and UV analyses
• To measure the UV absorption curves the emulsions
  were removed from the glass plates and dissolved
  into alcohol.
• SPF Determination - SAA Standard AS-2604.93.

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Formulation containing 2.0 BMDM, 5.0 Ethylhexyl
Salicylate, 15 Homosalate, 6 Oxybenzone and
7.5 EHMC
Absorbance Curve of Ethanol Solution of the
Emulsion Before After Irradiation
15 Loss _at_ 308 nm
40 Loss _at_ 357nm
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Formulation containing 2.0 BMDM, 5.0 Ethylhexyl
Salicylate, 15 Homosalate, 6 Oxybenzone and
7.5 EHMC with 4 of Corapan TQ
Absorbance Curve of Ethanol Solution of the
Emulsion Before After Irradiation
15 Loss _at_ 308 nm
40 Loss _at_ 357nm
93
Formulation containing 2.0 BMDM, 5.0 Ethylhexyl
Salicylate, 15 Homosalate, 6 Oxybenzone along
with 4 of Corapan TQ and reducing the EHMC to
4.0.
Absorbance Curve of Ethanol Solution of the
Emulsion Before After Irradiation
12 Loss _at_ 308 nm
28 Loss _at_ 357nm
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Formulation containing 2.0 BMDM, 5.0 Ethylhexyl
Salicylate, 15 Homosalate, 6 Oxybenzone along
with 4 of Corapan TQ and removing completely
the EHMC.
Absorbance Curve of Ethanol Solution of the
Emulsion Before After Irradiation
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• Study 4.2. - Conclusion.

• This data shows that when large amounts of
  EHMC are present in an emulsion which
  contains BMDM, the addition of Corapan TQ has
  little effect on the photostabilitv.
• Reducing the quantity of EHMC improves the
  stability, whereas removing it completely, while
  keeping the photostabilizer, confers very good
  protection.
• The Corapan TQ appears to contribute to a
  stabilising effect on the SPF when the EHMC is
  removed.