Technical Information

May 2005 Supersedes issue dated January 2004

Lutrol F 68

MEMP 030737e-01/Page 1 of 4

= Registered trademark of BASF Aktiengesellschaft

Poloxamer 188 for the pharmaceutical industry

Excipients Actives Contract Manufacturing Value Added

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Lutrol F 68

Chemical nature

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 9003-11-6

CAS No.

Description

White to slightly yellowish, waxy substance in the form of microbeads with a faint odour.

Specication

The current version of the product specications is available separately. Identity (IR spectrum) Hydroxyl value 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,% passes test 1115 7680 9510 # 1.0 6.07.5 #1 #5 #5 79.983.7 0.0180.034 # 10 5257 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-certied (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, parafn 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 emulsier 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].

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Lutrol F 68

In addition, Lutrol F 68 can also act as a co-emulsier in creams and emulsions and as a suspension stabilizer and tablet lubricant. Flow properties Aqueous solutions of Lutrol F 68 have ow properties of Newtonian uids 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 40C and the maximum viscosity between 60 and 75C (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 Fibre drums containing 102 kg (225 US lbs) Lutrol F 68 will still meet the specications after at least two years if stored in properly sealed containers at room temperature. 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 specic 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

Packaging

Stability and storage

Note

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Lutrol F 68

Literature

[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. DAmico, S. S. Davis, M. Frier, P. Hansrani, 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 Lokalansthetika mit Purinen und einigen makromolekularen Hilfsstoffen unter besonderer Bercksichtigung der in-vitro-Diffusion und der in-vivo-Resorption bei Fischen, Dissertation Freie Universitt Berlin 1980 [13] K.-H. Frmming, G.M. Ghaly, Arch. Pharm. 314, 926 (1981) [14] K.-H. Frmming, 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 Bioverfgbarkeit von schwerlslichen Arzneistoffen, dargestellt am Beispiel von Schmelzeinbettungen mit PEG 4000 und Pluronic F 68, Dissertation Freie Universitt Berlin 1980 [26] K.-H. Frmming, K. Heyer, R. Hosemann, Dtsch. Apoth. Ztg. 121, 2276 (1981) [27] K. Heyer, K.-H. Frmming, Dtsch. Apoth. Ztg. 123, 859 (1983) [28] M. Gyrgyne-Vago, M. Kata, G. Kedvessy, Acta Pharm. Hung. 54, 256 (1984)

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