Technical Information

Tretinoin

January 2010
Supersedes issue dated February 2009
03_030752e-06/Page 1 of 6

= Registered trademark of BASF group

USP, Ph. Eur.

Pharma Ingredients
& Services

03_030752e-06 January 2010

1. Medical indication

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Tretinoin

Tretinoin is a synthetic vitamin A acid derivative used for the treatment of severe
forms of acne, such as acne conglobata and acne cystica, which are mostly resistant
to other forms of treatment. Tretinoin is a stereoisomer of Isotretinoin.
Formulations for the treatment of acne are mostly creams, gels or solutions. Furthermore, there is also an oral formulation marketed for the treatment of special
forms of leukaemia.
A teratogenic effect in humans, as known for Isotretinoin, has not been reported
in published papers. However, there are publications reporting a teratogenic effect
in animals. Therefore, precautions must be taken if Tretinoin is to be used by women:
Contraceptive measures should be used starting one month before and ending
one month after treatment with Tretinoin. Tretinoin must not be administered during
pregnancy. All formulations of Tretinoin are prescription drugs.

Pharmacology

Tretinoin reduces the production of sebum in the skin and the size of the
sebaceous glands.

Pharmacokinetics

Absorption rates in topical application vary greatly, ranging between 0.5% and
25%, depending on the formulation and quantity applied on the skin. No detailed
data on Tretinoins kinetic profile is available.

2. Chemical information
Name

Tretinoin

Synonymous names

All-trans-vitamin A acid, all-trans-retinoic acid, all-A vitamin acid

CAS-No.

302-79-4

EINECS-No.

206-129-0

Structural formula

Empirical formula

C20H28O2

Molecular weight

300.44

3. Grades

PRD-No.
30035131

Tretinoin
0.43 kg
0.1 kg
0.01 kg (sample)

Retest period

See separate documentation: Q&R PI (not for regulatory purposes) available at

BASFs WorldAccount: https://worldaccount.basf.com (registered access).

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Tretinoin

4. Physical and chemical properties

Appearance

Yellow to yellowish-orange crystalline powder

Solubility

Water:

very sparingly soluble

Chloroform:

soluble

Methylene chloride:

soluble

Isopropanol:

soluble

Polyethylene Glycol:

soluble

5. Regulatory status

Meets current USP and Ph. Eur. monographs.

The open part of the DMF is available.

6. Safety aspects

Published papers suggest a high teratogenic potential of Tretinoin in animals.

Sale of dangerous substances:
It is unlawful to sell or offer for sale dangerous substance without indicating the
dangers relating to the substance in accordance with 3 a, Section 1.

7. Specification

See separate document: Standard Specification (not for regulatory purposes)

available via BASFs WorldAccount: https://worldaccount.basf.com (registered
access).

8. Storage conditions Store in air-tight containers below 25 C and protected from air and light.

Containers that have been opened must be kept under nitrogen or argon and
should be used up as quickly as possible. Once opened, containers must be
flushed with argon or nitrogen.

03_030752e-06 January 2010

9. Particle characterization

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Tretinoin

The particle size is measured by laser light diffractometry in an aqueous suspension.

Typical values of particle size distribution:

10. General information

on the processing of
Tretinoin

D 0.1

Min. 5 m

D 0.5

75 150 m

D 0.9

not larger than 450 m

Only peroxide-free pharmaceutical excipients should be used for the formulation.

Ingredients that tend to form peroxides should be strictly avoided.
Butylhydroxytoluene is recommended as an antioxidant.
Opened packages should be flushed with nitrogen or argon, tightly closed again
and used up as soon as possible.

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Tretinoin

11. Formulating examples

Tretinoin Cream (50 mg/100 g)

1. Formulation
I.

Tretinoin (BASF)
Luvitol EHO [1]
II. Cremophor A 6 [1]
Cremophor A 25 [1]
Glycerol monostearate
Cetyl alcohol
Tegiloxan 100 (Goldschmidt)
III. Butylhydroxytoluene
Propylene Glycol [1]
Preservatives
Perfumes
Water

0.05 g
8.0 g
3.0 g
1.5 g
3.0 g
3.0 g
0.5 g
0.04 g
4.0 g
0.5 g
0.2 g
76.2 g

2. Production
Separately prepare solution I and mixture II by heating to about 75 C.
Heat mixture III until a clear solution is formed.
Add solution I to the warm mixture II, then add mixture III and cool by stirring.

3. Chemical stability (2025 C, dark)

Months
0
3
6
9
12

Tretinoin content
0.046%
0.047%
0.046%
0.047%
0.047%

Loss of tretinoin
0%
0%
0%
0%

Analytical method: Spectrophotometric at 358 nm in chloroform +

2-propanol 1+1 (E 1%/1 cm = 1,480)

Tretinoin Gel (50 mg/100 g)

1. Formulation
I.

Tretinoin (BASF)
Ethanol
Cremophor RH 40 [1]
Perfume
Butylhydroxytoluene
II. Carbopol 940 (Goodrich)
Water
III. Triethanolamine
Water
2. Production
Prepare suspension II and add solution III to the well-stirred suspension.
When a clear mixture is formed, add solution I.

3. Properties
A clear yellowish gel is obtained.

0.05 g
15.0 g
1.0 g
q.s.
0.04 g
0.5 g
76.0 g
0.7 g
6.6 g

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Tretinoin + Dexpanthenol Gel (50 mg + 2,500 mg/100 g)

1. Formulation
I.

Tretinoin (BASF)
Lutrol E 400 [1]
Cremophor RH 40 [1]
Butylhydroxytoluene
II. Water
Dexpanthenol (BASF)
III. Lutrol F 127 [1]

Tretinoin

50.0 mg
5.0 g
6.0 g
40 mg
68.4 g
2.5 g
18.0 g

2. Production
Add II slowly to the clear solution I at about 40 C. Heat to about 50 C and dissolve
about 4 g of III in I/II. Cool to about 6 C and dissolve the rest of III. Keep cool until
the air bubbles disappear.

3. Properties
A clear yellowish gel is obtained.

4. Chemical stability (12 months, 23 C, dark)

Tretinoin
96%
Dexpanthenol
100%

5. Remark
It is important to protect the gel from light to prevent the isomerization and degradation
of Tretinoin.

Note

This document, or any answers or information provided herein by BASF, doesnot

constitute a legally binding obligation of BASF. While the descriptions, designs,data
and information contained herein are presented in good faith and believed to be
accurate, it is provided for your guidance only. Because many factors may affect
processing or application/use, we recommend that you make tests to determine
the suitability of a product for your particular purpose prior to use. It does not relieve
our customers from the obligation to perform a full inspection of the products upon
delivery or any other obligation. NO WARRANTIES OF ANY KIND, EITHER EXPRESS
OR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESS
FOR A PARTICULAR PURPOSE, ARE MADE REGARDING PRODUCTS DESCRIBED
OR DESIGNS, DATA OR INFORMATION SET FORTH, OR THAT THE PRODUCTS,
DESIGNS, DATA OR INFORMATION MAY BE USED WITHOUT INFRINGING THE
INTELLECTUAL PROPERTY RIGHTS OF OTHERS. IN NO CASE SHALL THE
DESCRIPTIONS, INFORMATION, DATA OR DESIGNS PROVIDED BE CONSIDERED
A PART OF OUR TERMS AND CONDITIONS OF SALE.
January 2010

BASF SE - Care Chemicals Division - Pharma Ingredients & Services - 67117 Limburgerhof - www.pharma-ingredients.basf.com