Process for the production of multiple w/o/w emulsions

A process for the production of multiple w/o/w emulsions in which PA1 a) a mixture of an oil and a lipophilic emulsifier I comprising glycerol and/or oligoglycerol or polyglycerol fatty acid esters is initially processed with intensive shearing to form a w/o pre-emulsion A, and PA1 b) the w/o pre-emulsion A is then further treated with an aqueous emulsifier II comprising adducts of ethylene oxide with fatty alcohols and/or sterols and, optionally, fatty alcohols, wherein the treatment is accompanied by gentle shearing; and to the resulting multiple w/o/w emulsions and their use in the preparation of cosmetic and pharmaceutical products.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to a process for the production of multiple w/o/w 
emulsions in which a w/o pre-emulsion is initially prepared with intensive 
shearing from water, an oil and an emulsifier I and the w/o pre-emulsion 
thus formed is subsequently treated with an aqueous emulsifier II with 
gentle shearing, to multiple w/o/w emulsions obtainable by this process 
and to the use of these multiple w/o/w emulsions for the production of 
cosmetic and pharmaceutical products. 
2. Statement of Related Art 
Multiple emulsions are emulsions of emulsions. Depending on their 
production process, they are either multiple water/oil/water (w/o/w) or 
oil/water/oil (o/w/o) emulsions. The most important application of 
multiple emulsions lies in the processing of active substances, which 
would otherwise be immiscible with one another, in a single formulation. 
Another advantage is that the active substances can be released under 
control over a prolonged period. Accordingly, multiple emulsions are of 
particular significance for the production of cosmetic and pharmaceutical 
products Cosm. Toil. 105, 65 (1990)!. 
A particularly suitable process for the production of multiple emulsions is 
described by S. Matsumoto in J. Coll. Interf. Sci. 57, 353 (1976). In this 
process, a pre-emulsion is initially prepared with intensive shearing at 
elevated temperature and is subsequently introduced into an aqueous 
solution of a hydrophilic emulsifier with gentle shearing at ambient 
temperature. Sorbitan monooleate and a polyethylene glycol derivative are 
used as the pair of emulsifiers. 
In addition, it is known from the extensive prior art that, basically, 
monoglycerides, sorbitan esters, polysorbates and highly ethoxylated fatty 
alcohols may be used as hydrophilic emulsifiers for the production of 
multiple emulsions, cf. the articles in Pharm. Acta. Helv. 66, 343 (1991), 
and by Seiller and Luca in Bull. Tech./Gattefosse Rep. 80, 27 (1987), S. 
T. P. Pharma 4, 679 (1988) and Int. J. Cosmet. Sci. 13, 1 (1991). 
In addition, w/o/w emulsions containing glycerol trifatty acid esters as 
oil component and hydrophilic polymers, such as gelatine for example, as 
stabilizer are known from Yakugaku Zasshi 112, 73 (1992). The use of 
albumin and polyacrylates as stabilizers for the water phase and nonionic 
surfactants for the oil phase is known from J. Controlled Release 3, 279 
(1986). Unfortunately, formulations such as these have proved to be 
inadequately stable in storage, particularly in the event of variations in 
temperature. 
Accordingly, a particular problem in the production of multiple emulsions 
lies in the choice of suitable pairs of emulsifiers which provide for 
adequate thermal stability, even in the event of prolonged storage. 
Another disadvantage is that mineral oils showing unfavorable 
biodegradability are normally used as the oil component. 
Accordingly, the problem addressed by the present invention was to provide 
a new process for the production of multiple w/o/w emulsions which would 
be free from the disadvantages mentioned above.

DESCRIPTION OF THE INVENTION 
The present invention relates to a process for the production of multiple 
w/o/w emulsions, in which 
a) a mixture of an oil and a lipophilic emulsifier I from the group of 
glycerol and/or oligoglycerol or polyglycerol fatty acid esters is 
initially processed with intensive shearing to form a w/o pre-emulsion A 
and 
b) the w/o pre-emulsion A is then further treated with an aqueous 
emulsifier II from the group of adducts of ethylene oxide with fatty 
alcohols and/or sterols and, optionally, fatty alcohols, the treatment 
being accompanied by gentle shearing. 
It has surprisingly been found that the multiple w/o/w emulsions obtainable 
by the process according to the invention remain stable in storage for 
long periods, even in the event of significant variations in temperature. 
The invention includes the observation that multiple emulsions with 
distinctly improved biodegradability in relation to the prior art can be 
made available through the choice of the oils mentioned and the absence of 
polymeric stabilizers. 
Oils 
Suitable oils for the production of the multiple w/o/w emulsions according 
to the invention are dialkyl cyclohexanes and dialkyl ethers. 
The dialkyl cyclohexanes are known substances which may be obtained by the 
relevant methods of preparative organic chemistry. One process for their 
production, for example, comprises subjecting aromatic dialkyl compounds 
(ortho-, meta-, para-xylene) from the BTX fraction of petroleum to 
catalytic hydrogenation. 
The dialkyl cyclohexanes suitable for use in accordance with the invention 
correspond to formula (I): 
EQU R.sup.1 --C--R.sup.2 (I) 
in which R.sup.1 and R.sup.2 independently of one another represent alkyl 
radicals containing 1 to 12 carbon atoms and C is a cyclohexyl radical. 
Typical examples are dimethyl cyclohexane, diethyl cyclohexane, 
methylethyl cyclohexane, dipropyl cyclohexane, di-n-butyl cyclohexane, 
ditert.butyl cyclohexane, di-2-ethylhexyl cyclohexane and, in particular, 
di-n-octyl cyclohexane. 
Dialkyl ethers are compounds corresponding to formula (II): 
EQU R.sup.3 --O--R.sup.4 (II) 
in which R.sup.3 and R.sup.4 independently of one another represent alkyl 
radicals containing 6 to 22 carbon atoms. 
Dialkyl ethers are also known substances which may be obtained by the 
relevant methods of preparative organic chemistry. Processes for their 
production, for example by condensation of fatty alcohols in the presence 
of p-toluenesulfonic acid, are known for example from Bull, Soc. Chim. 
France, 333 (1949), DE-A1 40 39 950 (Hoechst) and DE-A1 41 03 489 
(Henkel). Symmetrical dialkyl ethers containing 6 to 12 carbon atoms in 
the alkyl radicals are preferred from the applicational point of view. 
Dialkyl ethers of formula (II), in which R.sup.3 and R.sup.4 represent 
octyl and/or 2-ethylhexyl radicals, show particularly rapid emulsifying 
power. Accordingly, the particularly preferred dialkyl ethers according to 
the invention are di-n-octylether and di-2-ethylhexyl ether. 
The oils may be used in quantities of 10 to 30% by weight and preferably 15 
to 25% by weight, based on the pre-emulsion A. 
Emulsifier I 
Glycerol and/or oligoglycerol or polyglycerol esters may be used as the 
emulsifier I. Typical examples are technical monoesters and/or diesters of 
glycerol with fatty acids containing 12 to 22 carbon atoms, such as for 
example glycerol monolaurate, glycerol monopalmitate, glycerol 
monostearate, glycerol monoisostearate, glycerol monooleate and glycerol 
monobehenate. Other typical examples are monoesters and/or diesters of 
oligoglycerol or polyglycerol mixtures (degree of self-condensation 2 to 
20 and preferably 2 to 10) of the above-mentioned fatty acids containing 
12 to 22 carbon atoms, such as for example polyglycerol diisostearate or 
polyglycerol dioleate. It has proved to be of particular advantage to use 
mixtures of glycerol and oligoglycerol or polyglycerol esters, for example 
consisting of glycerol monooleate and triglycerol diisostearate (mixing 
ratio 80:20 parts by weight for example). The emulsifiers I may be used in 
quantities of 1 to 10% by weight and preferably 1 to 4% by weight, based 
on the pre-emulsion A. 
Emulsifier II 
Adducts of, on average, 20 to 50 and preferably 20 to 30 moles of ethylene 
oxide with fatty alcohols containing 16 to 22 and preferably 16 to 18 
carbon atoms may be used as emulsifier II. Typical examples are adducts 
of, on average, 25 to 30 moles of ethylene oxide with stearyl alcohol, 
isostearyl alcohol, oleyl alcohol, elaidyl alcohol, petroselinyl alcohol, 
linolyl alcohol, linolenyl alcohol, arachyl alcohol, gadoleyl alcohol, 
behenyl alcohol and erucyl alcohol and the technical mixtures thereof 
obtained, for example, in the high-pressure hydrogenation of native fatty 
acid methyl esters or aldehydes from Roelen's oxosynthesis. Adducts of, on 
average, 25 to 30 moles of ethylene oxide with technical cetostearyl 
alcohols are preferably used. 
Other emulsifiers which may be used are adducts of, on average, 10 to 40 
moles of ethylene oxide with sterols of vegetable and/or animal origin. By 
sterols are meant steroids containing 27 to 30 carbon atoms which only 
contain a hydroxy group at the C-3 and no other functional groups and 
which are often incorrectly termed stearins ROEMPP Chemie Lexikon, Vol. 
5, 1992, page 4302!. Typical examples are adducts of, on average, 10 to 40 
moles and preferably 25 to 30 moles of ethylene oxide with zoosterols, 
such as for example cholesterol, lanosterol, spongosterol or stellasterol, 
or phytosterols, such as for example ergosterol, stigmasterol and 
sitosterol. Adducts of, on average, 25 to 30 moles of ethylene oxide with 
soya sterol are particularly preferred. 
One preferred embodiment of the invention is characterized by the use of 
mixtures of adducts of, on average, 20 to 50 moles of ethylene oxide with 
fatty alcohols containing 16 to 22 carbon atoms and sterols of vegetable 
and/or animal origin. A typical example is a mixture of an adduct of, on 
average, 30 moles of ethylene oxide with cetostearyl alcohol and an adduct 
of, on average, 25 moles of ethylene oxide with soya sterol in a ratio by 
weight of 1:5 to 5:1 and preferably 2:1. The emulsifiers II may be used in 
quantities of 1 to 10% by weight and preferably 2.3 to 6.5% by weight, 
based on the multiple w/o/w emulsion. 
In one particular embodiment of the invention, fatty alcohols containing 12 
to 22 and preferably 16 to 18 carbon atoms may be added to emulsifier II 
as coemulsifiers, forming a liquid crystalline network in the emulsifier 
phase and contributing towards a further improvement in the stability of 
the resulting w/o/w emulsions. Suitable fatty alcohols are, for example, 
technical cetostearyl alcohols. The ratio by weight between emulsifier II 
and coemulsifier may be 1:1 to 1:2 and is preferably 1:1.5 to 1:1.8. 
Production of Pre-Emulsion A 
To produce the pre-emulsion, the oil is initially introduced into a stirred 
apparatus and the lipophilic emulsifier I is subsequently added. The 
components are homogenized with intensive shearing, i.e. at a stirrer 
speed of 1000 to 2000 r.p.m. and preferably 1200 to 1700 r.p.m. 
Centripetal turbines or, more particularly, colloid mills, for example, 
may be used as the stirred apparatus. It has proved to be of particular 
advantage to carry out the production of the pre-emulsion A at elevated 
temperature, i.e. at 50.degree. to 90.degree. C. and preferably at 
70.degree. to 80.degree. C. The homogenization time is normally between 5 
and 40 minutes and preferably between 10 and 30 minutes. In addition, it 
is advisable to add salt, preferably magnesium sulfate, to the 
pre-emulsion in quantities of 0.5 to 2% by weight, based on the 
pre-emulsion, for stabilization. 
Accordingly, the composition of the pre-emulsion A is typically 
a1) 10 to 30 (preferably 15 to 25)% by weight of oil; 
a2) 1 to 10 (preferably 1 to 4)% by weight of emulsifier I; 
a3) 0.5 to 2 (preferably 0.5 to 1)% by weight of salt; 
a4) ad 100% by weight water. 
The water content of pre-emulsion A is typically between 58 and 88.5% by 
weight and preferably between 70 and 83% by weight. 
Production of the Multiple w/o/w Emulsion 
To produce the multiple w/o/w emulsion, pre-emulsion A is initially 
introduced into a stirred apparatus and the aqueous emulsifier II is 
subsequently added. The pre-emulsion A may be used in quantities of 50 to 
90% by weight and preferably 65 to 80% by weight, based on the multiple 
w/o/w emulsion. The components are homogenized with gentle shearing, i.e. 
at a stirrer speed of 10 to 500 r.p.m. and preferably 150 to 250 r.p.m. 
Centripetal turbines or, more particularly, colloid mills may again be 
used as the stirred apparatus. It has proved to be of particular advantage 
to carry out the production of the multiple w/o/w emulsion at 20.degree. 
to 60.degree. C. and, more particularly, at 20.degree. to 25.degree. C. 
The homogenization time is typically between 5 and 50 mins. and preferably 
between 10 and 30 mins. 
Accordingly, the composition of the multiple w/o/w emulsion is typically 
b1) 50 to 90 (preferably 65 to 80)% by weight of pre-emulsion 
b2) 1 to 10 (preferably 2 to 7)% by weight of emulsifier II 
b3) 0 to 5 (preferably 1 to 4)% by weight of coemulsifier 
b4) balance ad 100% by weight water 
The water content of the multiple w/o/w emulsion (including the water 
content of pre-emulsion A) is typically between 57 and 93% by weight and 
preferably between 74 and 89% by weight. 
The present invention also relates to particularly storage-stable multiple 
w/o/w emulsions containing 
15 to 20% by weight of dioctyl cyclohexane 
1 to 5% by weight of triglycerol diisostearate/glycerol monooleate (4:1 
parts by weight) 
0.5 to 2% by weight of magnesium sulfate 
1 to 3% by weight of cetostearyl alcohol 30 EO adduct 
0.5 to 2% by weight of sterol 25 EO adduct 
1 to 4% by weight of cetostearyl alcohol ad 100% by weight water. 
Commercial Applications 
The multiple w/o/w emulsions obtainable by the process according to the 
invention are stable, even in the event of prolonged storage, and readily 
biodegradable. They are suitable for accommodating active substances which 
would otherwise be immiscible with one another and for the controlled 
delayed release thereof. 
Accordingly, the present invention also relates to the use of the multiple 
w/o/w emulsions obtainable by the process according to the invention for 
the production of cosmetic and pharmaceutical products, more particularly 
formulations for the cleaning and care of the hair and body, in which the 
multiple emulsions may be present in quantities of 1 to 99% by weight and 
preferably 10 to 50% by weight, based on the particular product. 
The following Examples are intended to illustrate the invention without 
limiting it in any way. 
EXAMPLES 
I Substances Used 
a) Oils 
a1) Cetiol.RTM. S, a product of Henkel KGaA, Dusseldorf, FRG Dioctyl 
cyclohexane 
a2) Cetiol.RTM. OE, a product of Henkel KGaA, Dusseldorf, FRG 
Dioctyl-n-octyl ether 
b) Emulsifier I 
b1) Dehymuls.RTM. B, Sidobre-Sinnova, Meaux, France Polyglycerol 
diisostearate, degree of condensation =5 
b2) Monomuls.RTM. 90-O-18, Chemische Fabrik Grunau, Illertissen, FRG 
Glycerol monooleate, monoglyceride content 90% by weight 
c) Emulsifier II 
c1) Mergital.RTM. E 1471, Sidobre-Sinnova, Meaux, France Cetostearyl 
alcohol 30 EO adduct 
c2) Generol.RTM. 122 E 25, Henkel KGaA, Dusseldorf, FRG Soya sterol 25 EO 
adduct 
Production Example 1 
1a) Pre-emulsion A: 
20 g of Cetiol.RTM. S and 4 g of Dehymuls.RTM. B were introduced into a 
centripetal turbine, after which a solution of 0.7 g of magnesium sulfate 
in 75 ml of water was added. The reaction mixture was then homogenized for 
10 minutes at 80.degree. C. at a speed of 1500 r.p.m. The speed was then 
reduced first to 1125 r.p.m. and then to 750 r.p.m., the reaction mixture 
being homogenized for another 10 minutes at those speeds. 
1b) Multiple w/o/w emulsion: 
77 g of pre-emulsion A were initially introduced, a solution of 2.1 g of 
Mergital.RTM. E 1471 and 1 g of Generol.RTM. 122 E 25 in 20 g of water was 
added over a period of 40 s and the whole was homogenized for 30 minutes 
at ambient temperature at a speed of 200 r.p.m. 
Production Example 2 
2a) Pre-emulsion A: 
20 g of Cetiol.RTM. OE and 4 g of Monomuls.RTM. 90-O-18 were introduced 
into a centripetal turbine, after which a solution of 0.7 g of magnesium 
sulfate in 75 ml of water was added. The reaction mixture was then 
homogenized for 10 minutes at 80.degree. C. at a speed of 1500 r.p.m. The 
speed was then reduced first to 1125 r.p.m. and then to 750 r.p.m., the 
reaction mixture being homogenized for another 10 minutes at those speeds. 
2b) Multiple w/o/w emulsion: 
77 g of pre-emulsion A were initially introduced, a solution of 2.1 g of 
Mergital.RTM. E 1471 and 1 g of Generol.RTM. 122 E 25 in 20 g of water was 
added over a period of 40 s and the whole was homogenized for 30 minutes 
at ambient temperature at a speed of 200 r.p.m. 
Production Example 3: 
3a) Pre-emulsion A: 
20 g of Cetiol.RTM. S and 4 g of Dehymuls.RTM. B were introduced into a 
centripetal turbine, after which a solution of 0.7 g of magnesium sulfate 
in 75 ml of water was added. The reaction mixture was then homogenized for 
10 minutes at 80.degree. C. at a speed of 1500 r.p.m. The speed was then 
reduced first to 1125 r.p.m. and then to 750 r.p.m., the reaction mixture 
being homogenized for another 10 minutes at those speeds. 
3b) Multiple w/o/w emulsion: 
60 g of pre-emulsion A were initially introduced, a solution of 1.4 g of 
Mergital.RTM. E 1471, 0.7 g of Generol.RTM. 122 E 25 and 3.52 g of 
cetostearyl alcohol in 34.4 g of water was added over a period of 40 s and 
the whole was homogenized for 30 minutes at 60.degree. C. at a speed of 
200 r.p.m.