Technical Information
Lutrol® F 68
May 2005 Supersedes issue dated January 2004
MEMP 030737e-01/Page 1 of 4
® = Registered trademark of BASF Aktiengesellschaft
■ ■ ■ ■
Excipients Actives Contract Manufacturing Value Added
Poloxamer Polox amer 188 for the pharma pharmaceu ceuti tical cal industry industry
MEMP 030737e-01 May 2005
Chemical nature
Lutrol ® F 68
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Polyoxyethylene-polyoxypropylene block copolymer of the general formula
where x = approx. 79 and y = approx. 28.
The percentage by weight of polyoxyethylene is approx. 80%.
INCI name
Poloxamer 188
CAS No.
9003-11-6
Description
White to slightly yellowish, waxy substance in the form of microbeads with a faint odour.
Specification
The current version of the product specifications is available separately. Identity (IR spectrum) Hydroxyl value
passes test 11–15
Molecular weight Water, % pH (2.5% in water) Ethylene oxide, ppm Propylene oxide, ppm 1,4-Dioxane, ppm Polyoxyethylene, wt. % Unsaturation, mEq/g Heavy metals, ppm Melting point, °C Appearance of the solution (20% in water) Sulfated ash,%
7680 – 9510 # 1.0 6.0–7.5 #1 #5 #5 79.9–83.7 0.018–0.034 # 10 52–57 clear, not darker than ref. sol. BY7 # 0.4
This product conforms to the requirements of the currently valid Ph. Eur. monograph on “Poloxamers” and the currently valid USP/NF monograph on “Poloxamer”. Lutrol® F 68 is also JPE-certified (Japanese Pharmaceutical Excipients). The test methods are described in the monographs. Solubility
Lutrol® F 68 is freely soluble in ethanol, freely soluble in water (opalescent solution), and is insoluble in diethyl ether, paraffin and fatty oils. Solubility in selected organic solvents:
Solubility in selected organic solvents: Methylene chloride Chloroform Acetonitrile Acetone Ethyl acetate Fields of application
approx. approx. approx. approx. approx.
35% 40% 20% 2% 1.5%
Lutrol® F 68 is used as an emulsifier and solubilizer, also in drug formulations for parenteral use [1 – 6]. Its solubilizing effect does not depend on the formation of micelles. Lutrol® F 68 is also used as a dispersing and wetting agent [7 –19], to prepare solid dispersions and to improve the solubility, absorption and bioavailability of low-solubility actives in solid oral dosage forms [20 – 23]. The materials are usually processed by melt granulation and spray granulation [24 – 28].
MEMP 030737e-01 May 2005
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Lutrol ® F 68
In addition, Lutrol® F 68 can also act as a co-emulsifier in creams and emulsions and as a suspension stabilizer and tablet lubricant. Flow properties
Aqueous solutions of Lutrol ® F 68 have flow properties of Newtonian fluids that change to non-Newtonian behaviour above a concentration of approx. 60%. Aqueous solutions containing more than 20% Lutrol ® F 68 are thermoreversible, i. e. the minimum viscosity is between 20 and 40°C and the maximum viscosity between 60 and 75°C (see Fig. 1). Repeated heating and cooling does not affect this property.
Fig. 1:
Viscosity of 20% and 25% aqueous solutions of Lutrol® F 68 as a function of temperature
The viscosity of Lutrol® F 68 solutions may be affected by the addition of electrolytes, humectants, alcohols, and tensides. Lutrol ® F 68 is not compatible with anionic tensides and low pH values.
Product No.
8-010293-1-53
Packaging
Fibre drums containing 102 kg (225 US lbs)
Stability and storage
Lutrol® F 68 will still meet the specifications after at least two years if stored in properly sealed containers at room temperature.
Note
The data contained in this publication are based on our current knowledge and experience. In view of the many factors that may affect processing and application of our product, these data do not relieve processors from carrying out their own investigations and tests; neither do these data imply any guarantee of certain properties, nor the suitability of the product for a specific purpose. Any descriptions, drawings, photographs, data, proportions, weights etc. given herein may change without prior information and do not constitute the agreed contractual quality of the product. It is the responsibility of the recipient of our products to ensure that any proprietary rights and existing laws and legislation are observed. May 2005
MEMP 030737e-01 May 2005
Literature
Page 4 of 4
Lutrol ® F 68
[1] A. C. Hymes, M. H. Safavian, A. Arbulu, P. Baute, J. Thorac. Cardiov. Surg. 56, 16 (1968) [2] A. C. Hymes, K. Beck, J. Thorac. Cardiov. Surg. 56, 23 (1968) [3] A. V. Prancan, B. Ecanow, R. J. Bernardoni, M. S. Sadove, J. Pharm. Sci. 69, 970 (1980) [4] K. M. D’Amico, S. S. Davis, M. Frier, P. Hans rani, J. G. Hardy, C. G. Wilson, Brit. J. Pharmacol. 72, 180P (1981) [5] D. Leu, B. Manthey, J. Kreiter, P. Speiser, P. P. DeLuca, J. Pharm. Sci. 73, 1433 (1984) [6] S.Y. Lin, Y. Kawashima, J. Parenter. Sci. Technol. 41, 83 (1987) [7] E. L. Parrott, V. K. Sharma, J. Pharm. Sci. 56, 1341 (1967) [8] S. M. Blaug, B. Hajratwala, J. Pharm. Sci. 63, 1240 (1974) [9] J. H. Collett, P. Wreglesworth, J. Pharm. Pharmacol. 27 (Suppl.), 9P (1975) [10] S. N. Malik, D. H. Canaham, M. W. Gouda, J. Pharm. Sci. 64, 987 (1975) [11] M. W. Gouda, S. El Gamal, A. R. Ebian, S. A. Khahil, Can. J. Pharm. Sci. 13, 16 (1978) [12] Ghaly Morcos Ghaly, „Wechselwirkungen von Lokalanästhetika mit Purinen und einigen makromolekularen Hilfsstof fen unter besonderer Berücksichtigung der in-vitro-Dif fusion und der in-vivo-Resorption bei Fischen“, Dissertation Freie Universität Berlin 1980 [13] K.-H. Frömming, G.M. Ghaly, Arch. Pharm. 314, 926 (1981) [14] K.-H. Frömming, G.M. Ghaly, Pharm. Ind. 43, 371 (1981) [15] S. Y. Lin, Pharm. Acta Helv. 60, 345 (1985) [16] K. Nakanishi, S. Miyazaki, T. Nadai, Yakuzaigaku 40, 42 (1980) [17] J. H. Collett, E. A. Tobin, J. Pharm. Pharmacol. 31, 174 (1979) [18] S. Y. Lin, Y. Kawashima, Pharm. Acta Helv. 60, 339 (1985) [19] L. W. Willits, E. A. Holstius, J. Amer. Pharm. Assoc. 17, 87 (1956) [20] R. K. Reddy, S. A. Khalil, M. W. Gouda, J. Pharm. Sci. 65, 1753 (1976) [21] R. K. Reddy, S. A. Khalil, M. W. Gouda, J. Pharm. Sci. 65, 115 (1976) [22] K. Stoll, H. Franz, Ger. Offen. 2. 627.706 (1978) [23] A. S. Geneidi, H. Hamacher, Pharm. Ind. 42, 315 (1980) [24] H. M. El-Banna, O.Y. Abdallah, Pharm. Acta Helv. 55, 256 (1980) [25] K. Heyer, „Physikalische und biopharmazeutische Untersuchungen zur Verbesserung der Bioverfügbarkeit von schwerlöslichen Arzneistof fen, dargestellt am Beispiel von Schmelzeinbettungen mit PEG 4000 und Pluronic F 68“, Dissertation Freie Universität Berlin 1980 [26] K.-H. Frömming, K. Heyer, R. Hosemann, Dtsch. Apoth. Ztg. 121, 2276 (1981) [27] K. Heyer, K.-H. Frömming, Dtsch. Apoth. Ztg. 123, 859 (1983) [28] M. Györgyne-Vago, M. Kata, G. Kedvessy, Acta Pharm. Hung. 54, 256 (1984)
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