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    03 - 030713e - Cremophor RH 40

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    03 - 030713e - Cremophor RH 40

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    icrao
    990 views8 pages
    emulsionante

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    03_030713e_Cremophor RH 40

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    990 views8 pages

    03 - 030713e - Cremophor RH 40

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    icrao
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    of 8

    Technical Information

    October 2010
    Supersedes issue dated November 2008

    Cremophor RH 40
    Macrogol-Glycerolhydroxystearat Ph. Eur
    Polyoxyl 40 Hydrogenated Castor Oil USP/NF

    03_030713e-09/Page 1 of 8

    = Registered trademark of BASF group

    For the pharmaceutical industry


    Cremophor RH 40 is a solubilizer for various hydrophobic APIs, fat-soluble
    vitamins, and essential oils.
    The use of Cremophor RH 40 grades in cosmetic preparations is the subject
    of a separate leaflet.

    Pharma Ingredients
    & Services

    03_030713e-09 October 2010

    Page 2 of 8

    Cremophor RH 40

    03_030713e-09 October 2010

    Page 3 of 8

    Cremophor RH 40

    Generic name

    Polyoxyl 40 Hydrogenated Castor Oil (USP, current edition),


    Macrogolglycerol Hydroxystearate (Ph.Eur., current edition).

    Chemical nature

    Cremophor RH 40 is a nonionic solubilizer and emulsifying agent obtained by


    reacting 1 mole of hydrogenated castor oil with 40 moles of ethylene oxide.
    The main constituent of Cremophor RH 40 is glycerol polyethylene glycol hydroxystearate, which, together with fatty acid glycerol polyglycol esters, forms the
    hydrophobic part of the product. The hydrophilic part consists of polyethylene
    glycols and glycerol ethoxylate.

    Properties

    Cremophor RH 40 is a white to yellowish paste at 20C. The HLB value lies between
    14 and 16.
    Particular features are that it has very little odour and in aqueous solutions is almost
    tasteless.

    Specification

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


    available via BASFs WorldAccount: https://worldaccount.basf.com (registered
    access).
    Unless stated otherwise, the analytical methods have been taken from the
    monographs Macrogolglycerol Hydroxystearate (Ph.Eur.) and Polyoxyl 40
    Hydrogenated Castor Oil (USP/NF). The product fulfills the requirements of
    these monographs.

    Regulatory status

    Meets the current Ph. Eur. monograph Macrogol-Glycerolhydroxystearat and


    the current USP/NF monograph Polyoxyl 40 Hydrogenated Castor Oil.

    Solubility

    Cremophor RH 40 forms clear solutions in water, ethanol, 2-propanol, n-propanol,


    ethyl acetate, chloroform, carbon tetrachloride, toluene and xylene.

    Solutions become cloudy as the temperature increases.

    Cremophor RH 40 can be mixed with all other Cremophors. At elevated temperatures


    it forms clear mixtures with fatty acids and fatty alcohols.

    Stability

    Pure Cremophor RH 40 is chemically very stable. Prolonged exposure to elevated


    temperatures can cause physical separation into a liquid and a solid phase on
    cooling but the product can be restored to its original form by homogenization.

    Cremophor RH 40 is stable in aqueous alcohol and purely aqueous solutions.


    However, it must be noted that s trong bases or acids should not be added, as
    otherwise the ester components may be saponified.

    Aqueous Cremophor RH 40 solutions can be sterilized by heating to 120 C.


    Allowance must be made for the fact that this can cause a slight decrease in
    the pH value. The phases may also separate during sterilization, but this can be
    remedied by agitating the solution while it is still hot.

    The preservatives normally used in the pharmaceuticals industry may be added


    to the aqueous solutions. The requisite concentrations should be determined in
    tests.

    Cremophor RH 40 is largely insensitive to water hardness.

    03_030713e-09 October 2010

    Page 4 of 8

    Cremophor RH 40

    Application
    Solubilization

    Aqueous solutions of vitamins A, D, E and K for oral and topical administration


    can be prepared with the aid of Cremophor RH 40. The fact that the solubilizer
    has very little taste or odour is an asset for such applications.

    In order to ensure that clear, aqueous solutions are obtained, the fatsoluble vitamins
    must first be intimately mixed with the solubilizer. Best results with vitamin A are
    obtained if it is in the form of vitamin A palmitate 1.7 million I.U./g, or vitaminA
    propionate 2.5 million I.U./g; or, in the case of vitamin K, if it is in the form of
    vitamin K1 (phytomenadione).

    As the method of preparing the solubilizate is very important, the production of a


    150000 I.U./ml aqueous vitamin A palmitate solution is d
    escribed in detail as a
    typical example:
    Vitamin A palmitate 1.7 million I.U./g
    Cremophor RH 40
    Water

    8.8 g
    25.0 g
    ad 100.0 ml

    The vitamin is mixed with Cremophor RH 40 and heated to 6065 C. Thewater,


    also heated to 6065 C, is added very slowly with thorough stirring into this mixture.
    As a result of hydration, the solution thickens, with the viscosity attaining a maxi
    mum after about half of the water has been added. Further addition of water
    then decreases the viscosity again. If the first half of the water is added too quickly,
    the solution can become opalescent. Alternatively, the warm mixture of the vitamin
    and Cremophor RH 40 can be slowly stirred into the water, which results in a smaller
    increase in viscosity.

    The following three diagrams demonstrate the use of Cremophor RH 40 for


    producing clear, highly concentrated, aqueous solutions of vitamin A palmitate,
    vitamin A propionate and vitamin E acetate.

    Fig. 1 Solubilization of vitamin A palmitate 1.7 million I.U./g

    03_030713e-09 October 2010

    Page 5 of 8

    Fig. 2 Solubilization of vitamin A propionate 2.5 million I.U./g

    Fig. 3 Solubilization of vitamin E acetate

    Cremophor RH 40

    03_030713e-09 October 2010

    Page 6 of 8

    Cremophor RH 40

    Likewise, the following vitamin quantities can be solubilized by a 6% Cremophor


    RH 40 solution.
    89 mg/ml Vitamin D2 (400000 I.U.), or
    5 mg/ml Vitamin D3 (125000 I.U.), or
    10 mg/ml Vitamin K1
    Less Cremophor RH 40 is usually required for mixtures of vitamins.
    A small addition of polyethylene glycol (Lutrol E 400), 1,2-propylene glycol or
    glycerol allows the preparation temperature and sometimes also the concentration
    of Cremophor RH 40 to be reduced.

    Miscellaneous
    solubilizer applications

    Clear, aqueous solutions of hydrophobic substances other than vitamins can be


    obtained with Cremophor RH 40. Examples are essential oils and certain drugs
    for oral and topical application. A feature of the solutions thus obtained is their
    good stability. The following substances serve as examples:
    Hexachlorocyclohexane

    Miconazole

    Hexeditine

    Gramicidin

    Levomepromazine

    Eucalyptol

    Thiopental

    Azulene

    Benzocaine

    Oil of anise

    Clotrimazole

    Oil of sage

    Diazepam

    Cremophor RH 40 shows little tendency to foaming, which is particularly important


    for solutions in aqueous ethanol. Further foam suppression can be obtained by
    the addition of a small quantity of Polypropylene Glycol 2000.

    Use as emulsifier

    Cremophor RH 40 is also very suitable as an emulsifying agent. It will emulsify a


    wide range of hydrophobic substances, e. g. fatty acids, fatty alcohols and drugs.

    Toxicity

    The toxicological abstract is available on request.


    Individual reports can be shared under secrecy agreement.

    Recommendations for product


    handling and sampling

    For proper product handling and sampling homogenization of the drum content
    is necessary. The new drums allow the repeated liquefaction of their content at
    around 60 C. It is recommended to use electrical drum heaters, heating covers
    or a heating chamber.

    03_030713e-09 October 2010

    Page 7 of 8

    Cremophor RH 40

    PRD-No.

    30455368

    Article-No.

    53048537

    Packaging

    PE-drums of 60 kg capacity.

    Storage

    The drums in which Cremophor RH 40 is stored should be kept tightly closed.

    The method of production employed for Cremophor RH 40 ensures that it is


    practically sterile. If the containers are repeatedly opened, microorganisms may
    grow in the product, particularly if the equipment used is not sterile.

    Retest date

    In the unopened original drums, the retest period for Cremophor RH 40 is at least
    2 years at room temperature (2025 C).

    Safety Data Sheet

    A Safety Data Sheet for Cremophor RH 40 is available.

    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.
    October 2010

    03_030713e-09 October 2010

    Page 8 of 8

    Cremophor RH 40

    BASF SE - Nutrition & Health - Pharma Ingredients & Services - 67117 Limburgerhof - www.pharma-ingredients.basf.com

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