Cremophor Elp

Technical Information

Cremophor ® ELP

May 2007 Supersedes issue dated November 2005 MEMP 030712e-05/Page 1 of 4

® = Registered trademark of BASF Aktiengesellschaft

Solu­bi­liser for the phar­ma­ceu­ti­cal indus­try

Excipients s Contract Manufacturing Value Added

MEMP 030712e-05 May 2007



Page  of 4

Cremophor ELP

Cremophor ELP, a pur­i­fied grade of Cremophor EL was spe­cially devel­oped for sen­si­ tive ­active ingre­dients, as the ­higher pur­ity was found to ­improve their stabil­ity.

Chem­i­cal ­nature Like Cremophor EL, Cremophor ELP is a non­ionic solu­bi­liser made by react­ing cas­tor oil with eth­y­lene oxide in a molar ratio of 1 : 35. This is fol­lowed by a pur­ifi­ca­tion pro­cess. Descrip­tion ­Unlike Crem­o­phor® EL, Cremophor ELP is a white to yel­low­ish paste or ­cloudy liq­uid. It has to ful­fill more exact­ing require­ments with ­regard to water con­tent, potas­sium ions and free fatty acids, par­tic­u­larly ricin­o­leic, oleic and pal­mitic acids. On heat­ing, the last solid con­stit­u­ents melt at 26 °C to yield a clear oily liq­uid with a weak but char­ac­ter­is­tic odour. The HLB value lies ­between 12 and 14. The crit­i­cal ­micelle con­cen­tra­tion (CMC) lies at ­approx. 0.02%. ­Pharmacopœias Cremophor ELP meets the require­ments of the current Ph.Eur. Mono­graph, “Macrogolglycerol Ricinoleate”. It also con­forms to the latest mono­graph, “Poly­oxyl 35 Cas­tor Oil”. Sol­u­bil­ity Cremophor ELP forms clear solu­tions in water and also dis­solves in a wide range of ­organic sol­vents, such as eth­a­nol, n-prop­a­nol, iso­prop­a­nol, ethyl ace­ tate, chlo­ro­form, car­bon tet­ra­chlo­ride, tri­chlo­ro­eth­y­lene, ­toluene and ­xylene. Spec­ifi­ca­tion

Appear­ance Iden­tifi­ca­tion Alka­lin­ity Sapon­ifi­ca­tion value Acid value ­Hydroxyl value ­Iodine value Water pH (10% in water) Eth­y­lene oxide 1,4-diox­ane Clar­ity (10 % in water) ­Colour (10 % in water) Den­sity (25 °C) Vis­cos­ity (25 °C) Sul­phated ash (USP-NF) Ash (Ph.Eur.) Heavy met­als Potas­sium Free fatty acids (C12–C18) (GC) Ricin­o­leic acid (HPLC) Oleic acid (HPLC) Pal­mitic acid (HPLC)

White to ­slightly yel­low­ish paste Con­forms Con­forms 65–70  2.0 65–78 25–35  0.5% 5.0 – 7.0  1  10 ppm Con­forms max. BY6 1.05–1.06 g/ml 600–750 mPa · s  0.2 %  0.2 %  10 ppm  15 ppm  1.0%  0.2%  0.1%  0.1%

MEMP 030712e-05 May 2007

Page  of 4

Resid­ual sol­vents (Ph. Eur. 5.4):

Micro­bi­o­log­i­cal Status (Cat. 2 + 3 a)

Cremophor ELP

Only the Class ll sol­vents, eth­y­lene gly­col, and 1,4-diox­ane, and Class III sol­vents are ­likely to be ­present. Resid­ual eth­y­lene gly­col is below the ­Option 1 limit of 620 ppm. Resid­ual 1,4 diox­ane is below the ­Option 1 limit of 380 ppm and is sep­ar­ ately spec­i­fied. Resid­ual Class III sol­vents are below 0.5%. Con­forms

Unless oth­er­wise indi­cated, the meth­ods used to deter­mine the fig­ures ­quotedabove are those given in the Ph.Eur. mono­graph, “Macrogolglycerol Ricinoleate” and USP-NF mono­graph, “Poly­oxyl 35 Cas­tor Oil”. Appli­ca­tions One pos­sible field of appli­ca­tion that can be con­sid­ered for Cremophor ELP is in paren­teral dos­age forms. Thus Cremophor ELP is suit­able for par­tic­u­larly demand­ing for­mu­la­tions, which prove not to achieve the desired stability when Cremophor EL is used. For other inject­ables, we rec­om­mend Sol­u­tol® HS 15 as a solu­bi­liser. For fur­ther infor­ma­tion, ­please see the Tech­ni­cal Data ­Sheets for Cremophor EL and Sol­u­tol HS 15. Tox­i­col­ogy No tox­i­co­log­i­cal stud­ies have been car­ried out on Cremophor ELP ­itself. ­Please refer to the tox­i­co­log­i­cal find­ings for Cremophor EL. PBG-Number

10205104

PRD-Number

30035162

Pack­ag­ing

60-kg remov­able-head steel drum with a Lupo­len® ­inliner with its own lid.

Stor­age Cremophor ELP ­should be ­stored in ­tightly ­closed con­tain­ers pro­tected from light. Prolonged storage is not recommended unless the containers are completely full. ­Shelf life Crem­o­phor® ELP is ­stable for at least 24 ­months if ­stored in the ­unopened orig­i­nal con­tain­ers at room tem­per­a­ture (max. 25 °C). Safety Data Sheet

A ­Safety Data Sheet is avail­able for Cremophor ELP.

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 2007

MEMP 030712e-05 May 2007

BASF Aktiengesellschaft

Page  of 4

Fine Chemicals Division - Pharma Solutions - 67117 Limburgerhof - www.pharma-solutions.basf.com

Cremophor ELP