Drometrizole trisiloxane

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Name
Drometrizole trisiloxane
Accession Number
DB11585
Type
Small Molecule
Groups
Approved
Description

Drometrizole trisiloxane is a photostable UVA and UVB light filter 1,3,4,5,6,9. The compound is a lipophilic benzotriazole derivative marketed as Meroxyl XL by L'Oreal, although sunscreens with drometrizole trisiloxane are currently only approved for use in the EU, Canada, Australia, and Japan, among other countries.

Despite being used elsewhere in the world with relatively few reports of adverse reactions, the FDA continues to cite that the existing scientific record is not sufficient to establish the compound as being generally recognized as safe and effective for over-the-counter sunscreen use 8,10.

Structure
Thumb
Synonyms
  • Silatrizole
External IDs
OR 10154 / OR-10154
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
45 SPF High Protection Uva Uvb CreamDrometrizole trisiloxane (3.0 %) + Avobenzone (3.5 %) + Ecamsule (2.0 %) + Octocrylene (10 %) + Titanium dioxide (3.3 %)CreamTopicalLaboratoires La Roche Posay Canada2008-04-162016-08-31Canada
60 SPF Stick Protection Ciblee Uva Uvb Anthelios XLDrometrizole trisiloxane (2.00 %) + Avobenzone (3.00 %) + Octocrylene (10.00 %) + Titanium dioxide (6.25 %)StickTopicalLaboratoires La Roche Posay Canada2007-04-12Not applicableCanada
Anthelios Dermo-kidsDrometrizole trisiloxane (4.5 %) + Avobenzone (3 %) + Ecamsule (1.5 %) + Octisalate (5 %) + Octocrylene (2.5 %) + Titanium dioxide (5.85 %)LotionTopicalLaboratoires La Roche Posay Canada2015-05-04Not applicableCanada
Anthelios SPF 45Drometrizole trisiloxane (0.5 %) + Avobenzone (3.0 %) + Bemotrizinol (0.5 %) + Ecamsule (1.0 %) + Octisalate (5.0 %) + Octocrylene (5.0 %) + Titanium dioxide (4.7 %)LotionTopicalLaboratoires La Roche Posay Canada2010-05-042015-08-07Canada
Anthelios Spray SPF 45Drometrizole trisiloxane (1.5 %) + Avobenzone (4.0 %) + Bemotrizinol (3.0 %) + Ecamsule (1.0 %) + Octisalate (5.0 %) + Octocrylene (3.5 %) + Titanium dioxide (2.6 %)SprayTopicalLaboratoires La Roche Posay Canada2010-05-04Not applicableCanada
Anthelios XL Cream SPF 60Drometrizole trisiloxane (3.00 %) + Avobenzone (3.50 %) + Ecamsule (3.00 %) + Octocrylene (10.00 %) + Titanium dioxide (4.15 %)CreamTopicalLaboratoires La Roche Posay Canada2007-04-12Not applicableCanada
Anthelios XL Melt-IN CreamDrometrizole trisiloxane (3 %) + Avobenzone (4 %) + Bemotrizinol (5 %) + Ecamsule (0.5 %) + Octisalate (5 %) + Octocrylene (7 %) + Titanium dioxide (2.5 %)CreamTopicalLaboratoires La Roche Posay CanadaNot applicableNot applicableCanada
AntherposDrometrizole trisiloxane (1.0 %) + Avobenzone (2.0 %) + Ecamsule (1.0 %) + Octocrylene (10 %) + Titanium dioxide (3.3 %)CreamTopicalLaboratoires La Roche Posay Canada2008-04-162012-08-03Canada
Anti-brillance Lotion Toucher SecDrometrizole trisiloxane (0.5 %) + Avobenzone (3 %) + Homosalate (15 %) + Octisalate (5 %) + Octocrylene (7 %)LotionTopicalVichy CanadaNot applicableNot applicableCanada
Anti-shine Anthelios XL Dry Touch Gel-creamDrometrizole trisiloxane (0.5 %) + Avobenzone (3 %) + Homosalate (15 %) + Octisalate (5 %) + Octocrylene (7 %)CreamTopicalLaboratoires La Roche Posay CanadaNot applicableNot applicableCanada
International/Other Brands
Mexoryl XL
Categories
UNII
HC22845I1X
CAS number
155633-54-8
Weight
Average: 501.849
Monoisotopic: 501.229921733
Chemical Formula
C24H39N3O3Si3
InChI Key
HUVYTMDMDZRHBN-UHFFFAOYSA-N
InChI
InChI=1S/C24H39N3O3Si3/c1-18-14-20(15-19(2)17-33(9,29-31(3,4)5)30-32(6,7)8)24(28)23(16-18)27-25-21-12-10-11-13-22(21)26-27/h10-14,16,19,28H,15,17H2,1-9H3
IUPAC Name
2-(2H-1,2,3-benzotriazol-2-yl)-4-methyl-6-[2-methyl-3-(2,2,4,6,6-pentamethyl-3,5-dioxa-2,4,6-trisilaheptan-4-yl)propyl]phenol
SMILES
CC(CC1=C(O)C(=CC(C)=C1)N1N=C2C=CC=CC2=N1)C[Si](C)(O[Si](C)(C)C)O[Si](C)(C)C

Pharmacology

Indication

Drometrizole trisiloxane is used as an active ingredient in various sunscreens for the indication of protecting the skin by absorbing the damaging UV radiation of sunlight 1,3,4,5,6,9,10.

Associated Conditions
Pharmacodynamics

As an active ingredient in sunscreen products, drometrizole trisiloxane is applied directly onto human skin where it acts as a chemical sunscreen layer between skin and sunlight that also directly absorbs the UV sunlight radiation 1,3,4,5,6,9. Since drometrizole trisiloxane is also considered to have little to no absorption through the skin 1,3,4,5,6,9, little systemic exposure and pharmacokinetics are expected and users can freely wash off and re-apply the compound as necessary.

Mechanism of action

Ultraviolet radiation is the invisible energy component to sunlight and consists of three wavelength ranges:

(a) UVA is long-range UV radiation between 320-400nm 7. Although not as energetic as UVB, UVA can penetrate deep into the dermis 7. UVA can cause immediate tanning, premature skin aging, and can also play a role in the formation of some skin cancers 7. Approximately 95% of UVA from the sun passes through Earth's ozone layer 7.

(b) UVB is short-wavelength UV radiation between 280-320nm 7. It is capable of penetrating the outer protective layer of the skin and is responsible for delayed tanning, sunburns, and most skin cancers 7. A large amount of UVB is absorbed by the ozone layer, however, as only 5% reaches the Earth's surface 7.

(c) UVC is comprised of wavelengths between 100-280nm and is very energetic 7. It is very dangerous to all forms of life, even when the exposure is short 7. However, UVC radiation is generally filtered out by the ozone layer and never reaches the Earth 7.

Ultimately, the shorter the wavelength, the more harmful the UV radiation - although shorter wavelength UV radiation is less able to penetrate the skin 7.

Subsequently, drometrizole trisiloxane is a broad spectrum lipophilic benzotriazole derivative chemical sunscreen that is capable of absorbing UVA and UVB radiation 1,3,4,5,6. It is also photostable, meaning that it will not degrade in the presence of sunlight, unlike other UV filters like the widely used UVA absorber avobenzone 6. When combined with the UV blocker ecamsule, it has been shown that the two UV blockers elicit a synergistic effect involving an enhanced protective action for the skin against UVA and UVB radiation 1,3,4,5,6. Additionally, drometrizole trisiloxane is usually combined with other active sunscreen agents like titanium dioxide, avobenzone, and others to ensure the combined product covers or protects against as broad a spectrum of UV radiation as possible, considering drometrizole trisiloxane does not absorb against the entire range of UV radiation 6.

And finally, at the molecular level, it is believed that the general structure of various UV blockers like drometrizole trisiloxane as aromatic molecules conjugated with carbonyl groups is capable of absorbing high energy ultraviolet rays and then consequently releasing that energy as less harmful, lower energy rays.

Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more
Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more
Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more
Absorption

Drometrizole trisiloxane is reported as having little to no absorption through the skin 3,6. At this time, however, studies demonstrate that the components of most commonly used sunscreens are likely absorbed into the skin at least to some extent - although penetration to deeper tissues and the cutaneous circulation remains limited 2. Despite the extensive use of sunscreen products around the world, there have been few reports of adverse effects related to their use 2.

Volume of distribution

Drometrizole trisiloxane is reported as having little to no absorption through the skin 3,6. The systemic presence of the compound is consequently expected to be minimal.

Protein binding

Drometrizole trisiloxane is reported as having little to no absorption through the skin 3,6. The systemic presence of the compound is consequently expected to be minimal.

Metabolism

Drometrizole trisiloxane is reported as having little to no absorption through the skin 3,6. The systemic presence of the compound is consequently expected to be minimal.

Route of elimination

Drometrizole trisiloxane is reported as having little to no absorption through the skin 3,6. The systemic presence of the compound is consequently expected to be minimal.

Half life

Drometrizole trisiloxane is reported as having little to no absorption through the skin 3,6. The systemic presence of the compound is consequently expected to be minimal.

Clearance

Drometrizole trisiloxane is reported as having little to no absorption through the skin 3,6. The systemic presence of the compound is consequently expected to be minimal.

Toxicity

Drometrizole trisiloxane is reported as having little to no absorption through the skin, which leads most national health agencies that approve its use in sunscreens (including the EU, Canada, Australia, Japan, and other countries) to consider it safe, given that most of their toxicity studies return little risk of adverse reactions as well 1,3,4,5,6,9.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Gonzalez S, Fernandez-Lorente M, Gilaberte-Calzada Y: The latest on skin photoprotection. Clin Dermatol. 2008 Nov-Dec;26(6):614-26. doi: 10.1016/j.clindermatol.2007.09.010. [PubMed:18940542]
  2. Benson HA: Assessment and clinical implications of absorption of sunscreens across skin. Am J Clin Dermatol. 2000 Jul-Aug;1(4):217-24. [PubMed:11702366]
  3. Dermascope: The State of Sunscreen Innovation in 2015 [Link]
  4. Skin Therapy Letter: Update on Sunscreens [Link]
  5. Current Trends in Photoprotection - A New Generation of Oral Photoprotectors [Link]
  6. PhaMix: Mexoryl SX/XL Sunscreens [Link]
  7. Government of Canada: What is ultraviolet radiation? [Link]
  8. Chemical & Engineering News: After More Than A Decade, FDA Still Won't Allow New Sunscreens [Link]
  9. Health Canada: Sunscreen Monograph [File]
  10. FDA Drometrizole Trisiloxane Safety Assessment Denial Letter [File]
External Links
ChemSpider
8024601
Wikipedia
Drometrizole_trisiloxane
MSDS
Download (186 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentMelasma1
Not AvailableCompletedDiagnosticDermatitis, Photocontact1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SprayTopical
CreamTopical
StickTopical
AerosolTopical
GelTopical
LotionTopical
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000703 mg/mLALOGPS
logP6.5ALOGPS
logP7.25ChemAxon
logS-5.8ALOGPS
pKa (Strongest Acidic)9.96ChemAxon
pKa (Strongest Basic)-0.38ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.4 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity137.97 m3·mol-1ChemAxon
Polarizability54.24 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenyl-1,2,3-triazoles. These are organic compounds containing a 1,2,3-triazole substituted by a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Triazoles
Direct Parent
Phenyl-1,2,3-triazoles
Alternative Parents
Siloxanes / Phenylpropanes / Benzotriazoles / Para cresols / Toluenes / Trialkylheterosilanes / Heteroaromatic compounds / Organic metalloid salts / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Phenyl-1,2,3-triazole / Benzotriazole / Siloxane / Phenylpropane / P-cresol / Phenol / Toluene / Monocyclic benzene moiety / Benzenoid / Trialkylheterosilane
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Drug created on April 27, 2016 16:34 / Updated on July 13, 2019 00:57