Technical Information Lutrol® F 127

August 2005
Supersedes issue dated May 2005

MEMP 030738e-01/Page 1 of 8

® = Registered trademark of Poloxamer 407

BASF Aktiengesellschaft
Thickening agent and gel former for the pharmaceutical industry

Excipients
s
Contract Manufacturing
Value Added
MEMP 030738e-01 August 2005 Page  of 8 Lutrol® F 127

Chemical nature Polyoxyethylene polyoxypropylene block copolymer of the general structure:

where a is approx. 101 and b is approx. 56.

The percentage by weight of polyoxyethylene is approx. 70%.

CTFA name Poloxamer 407

CAS No. 9003-11-6

Description White, coarse-grained powder with a waxy consistency. Contains BHT.

Specifications The current version of the product specifications is available separately.

Molecular weight calculated on the OH value 9840 to 14,600 g/mol

Percentage of polyoxyethylene by weight 73.2 1.7%
pH value (2.5% in water) 5.0 – 7.5
Unsaturation 0.048 0.017 mEq/g
Heavy metals max. 20 ppm
Volatile organic compounds conforms
Ethylene oxide max. 1 ppm
Propylene oxide max. 5 ppm
1,4-Dioxane max. 5 ppm

This product conforms to the requirements of the currently valid Ph. Eur.
monograph on “Poloxamers” and the USP/NF monograph on “Poloxamer”.

Lutrol® F 127 is JPE-certified (Japanese Pharmaceutical Excipients).

The test methods are described in the monographs.

Solubility Lutrol® F 127 is soluble in water, ethanol (95%) and isopropanol. It is insoluble in
ether, paraffin and fatty oils.

Fields of application Lutrol® F 127 is used primarily as a thickening agent and gel former, but also
as a co-emulsifier and consistency enhancer in creams and liquid emulsions.
It is also used as a solubilizer for certain active substances such as nifedipine,
naproxen and fenticonazole as well as for essential oils in pharmaceutical and
cosmetic formulations. Moreover, Lutrol® F 127 is suitable for the formulation
of active substances that show reduced solubility as a result of neutralization.
Owing to its ability to affect viscosity, Lutrol® F 127 is suitable as a stabilizer
for topically and orally administered suspensions. Lutrol® F 127 is also used in
toothpastes, gargles and mouthwashes.

Preparation of gels Gels may generally be prepared by two methods:

1. “Cold process”
Lutrol® F 127 is dissolved completely in water at room temperature or water
pre-cooled to approx. 5°C. Active substances that are insoluble in water
are dissolved in ethanol, isopropanol or propylene glycol and mixed with the
aqueous phase at 5°C to form a homogeneous mass.

2. “Hot process”
Lutrol® F 127 is dissolved in water at approx. 70°C. Active substances that are
insoluble in water are dissolved in ethanol, isopropanol or propylene glycol at
70°C and mixed with the warm aqueous phase to form a homogeneous mass.
The gel forms when the solution cools to room temperature.
MEMP 030738e-01 August 2005 Page  of 8 Lutrol® F 127

Both methods of preparation will generally yield gels with comparable properties.
Adding Lutrol® F 127 too rapidly to the hot aqueous phase may result in the
formation of lumps that will only dissolve after standing for several hours. Any
loss of solvent must be replaced, otherwise a thixotropic effect is observed.

We recommend using the “cold process” for the preparation of gels, particularly
if the active substance is sensitive to heat. In order to prevent the formation of air
bubbles, a vacuum should be applied before heating, i.e. before the gel forms.

Flow properties Dilute aqueous solutions have flow properties of Newtonian fluids that change to
non-Newtonian behaviour with a pronounced pour point at concentrations of
above approx. 15%. (Fig. 1).

Fig. 1 Flow properties of 10% and 25% aqueous Lutrol® F 127 gel

Lutrol® F 127 gels are thermoreversible. They exhibit maximum viscosity in the
30 – 60°C range. The sol-gel transition temperatures of aqueous Lutrol® F 127
solutions of different concentrations as well as their viscosity as a function of
temperature are shown in Fig. 2.

The viscosity of Lutrol® F 127 gels may be affected by the addition of electrolytes,
moisturizers, alcohols and surfactants. Thus, the addition of more than 1% sodium
chloride reduces the gel formation temperature as well as the viscosity and pour
point (Fig. 3). Similar effects are also seen with potassium chloride. In contrast to
this, ethanol increases the gel formation temperature. The use of anionic surfactants
may inhibit gel formation, even at Lutrol® F 127 concentrations of over 20%. This
is true, for example, for sodium lauryl sulphate at concentrations above 2%. Low
pH values affect both the gel formation temperature and the viscosity.
MEMP 030738e-01 August 2005 Page  of 8 Lutrol® F 127

Fig. 2 Viscosity of aqueous Lutrol® F 127 gels as a function of temperature

Fig. 3 Pour point of 25% aqueous Lutrol® F 127 gels at different NaCl levels
(temp. 25°C)
MEMP 030738e-01 August 2005 Page  of 8 Lutrol® F 127

The sol-gel transition temperature can be influenced by combining Lutrol® F 127

with other poloxamers and, in some cases, it is possible to obtain very narrow gel
formation temperature ranges. Moreover, gels formed from mixtures of Lutrol® F 127
and Lutrol® F 68 exhibit no reduction in viscosity with increasing temperature over
a wide range. Figure 4 illustrates the changes in viscosity of the two formulations
described below:

Excipient Formulation 1 Formulation 2

Lutrol® F127 20% 15%
Lutrol® F 68 20% 20%

Fig. 4 Viscosity profile of gels prepared from poloxamer mixtures as a function of

temperature

Formulation examples Lutrol® F 127 gel

Active substance xg
Propylene glycol 20.0 g
Lutrol® F 127 22.0 g
Purified water 58.0 g
Description: clear, colourless gel.

Lutrol® F 127/F 68 gel

Active substance xg
Propylene glycol 20.0 g
Lutrol® F 127 22.0 g
Lutrol® F 68 5.0 g
NaCl 1.0 g
Water 51.0 g
Description: clear, colourless gel.

Examples of Lutrol® F 127 formulations with active substances can be taken from
our compendium “Generic Drug Formulations”. The compendium is available as
a loose-leaf folder or on CD-ROM and can be obtained from the regional BASF
representatives.
MEMP 030738e-01 August 2005
PBG No. 10 096 034
Packaging Fibre drums containing 90 kg (200 US lbs)
Stability and storage The material is stable for two years when stored in properly sealed containers at
Literature
Reviews/gen. information
Gel formation/influencing factors
Enhancement of stability of drug
formulations
Enhancement of solubility
Page  of 8 Lutrol® F 127
room temperature.
Schmolka, Irving R.
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MEMP 030738e-01 August 2005
Drug formulations for percutaneous
administration
(Till now only scientific applications)
Drug formulations for intramuscular
administration
(Till now only scientific applications)
Drug formulations for intraperitoneal
administration
(Till now only scientific applications)
Drug formulations for subcutaneous
administration
Drug formulations for oral administration Tayel, S.; Osman, A.
Page  of 8 Lutrol® F 127
Suh, Hearan; Jun, H.W.
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MEMP 030738e-01 August 2005 Page  of 8 Lutrol® F 127

Ophthalmic formulations
Formulations for dental use
Portoles, Marta; Refojo, Miguel F.; Leong, Fee Lai
J. Biomed. Mater. Res. (1994), 28 (3), 303-9
Viegas, Tacey X.; Reeve, Lorraine E.; Levinson, Robert S.;
Patent: US 5300295 A-940405, Applicator: Mediventures, Inc., USA
Bochot, A.; Fattal, E.; Grossiord, J.-L.; Puisieux, F.; Couvreur, P;
World Meet. Pharm., Biopharm. Pharm. Technol., 1st (1995), 557-8
Publisher: APGI, Chatenay Malabry, Fr. CODEN: 62JJAQ
Esposito, E.; Carotta, V.; Scabbia, A.; Trombelli, L.; D’Antona, P.;
Menegatti, E.; Nastruzzi, C.
Int. J. Pharm. (1996), 142 (1), 9-23

Nanoparticles Florence, Alexander T.; Hillery, Anya M.; Hussain, Nasir; Jani, Praful U.
J. Controlled Release (1995), 36 (1-2), 39-46

Combinations with polymers Xu, Xin; Lee, Ping I.

Pharm. Res. (1993), 10 (8), 1144-52

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.

August 2005

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