AU3961100A

AU3961100A - Method for producing cosmetic or pharmaceutical formulations by means of a micromixture directly before use

Info

Publication number: AU3961100A
Application number: AU39611/00A
Authority: AU
Inventors: Joachim Bunger; Hans-Jurgen Driller; Annette Wagner; Jutta Zur Lage
Original assignee: Merck Patent GmbH
Current assignee: Merck Patent GmbH
Priority date: 1999-03-17
Filing date: 2000-03-07
Publication date: 2000-10-04
Anticipated expiration: 2020-03-07
Also published as: EP1161221A1; WO2000054735A1; AU768399B2; DE19911777A1; CA2367391A1; CN1344145A; JP2002538947A

Description

Process for the preparation of cosmetic or pharmaceutical formulations using a micromixer 5 The present invention relates to a process for the preparation of cosmetic or pharmaceutical formulations immediately before use, in which two or more liquid components from separate stock chambers are mixed inti mately with one another by passing the liquid components through a micromixer. The present invention furthermore relates to the lotions, 10 emulsions, gels, creams and solutions prepared by the process according to the invention, either for cosmetic use or, if corresponding pharmaceuti cal active ingredients have been incorporated, to the pharmaceutical formulations prepared. 15 Various processes for mixing a plurality of substances as intimately as possible are used for the preparation of cosmetic products. Depending on the mixing intensity necessary, use is made of one or more processes for combining substances, which can take place successively or in parallel. In chemical process technology, the term mixing is taken to mean per se 20 basic operations which serve for very substantial homogenisation of substances. The aim is to combine substance streams in such a way that the most uniform composition possible of the individual components is obtained in part-volumes of the resultant mixture. 25 A special form of mixing is homogenisation. This is taken to mean mixing of phases which are immiscible with one another. Accordingly, the term homogenisation is taken to mean a change in the state of distribution and the particle size of the internal phase of emulsions and suspensions, so that, in microscopic terms, a homogenous system is formed and the 30 distributed phase does not settle out or cream up without the action of external forces. The term dispersion is taken to mean mixing of a substance system consisting of two (or more) phases, in which one substance (disperse 35 phases) is distributed (dispersed) in extremely fine form in another substance (dispersion medium). Both the particles of the disperse phase -2 and the dispersion medium may be solid, liquid or gaseous. Examples of dispersions are aerosols, emulsions, suspensions and colloids. Another type of mixing which is conventional in the preparation of 5 cosmetics is emulsification. This is taken to mean mixing of two liquids which are insoluble or only sparingly soluble in one another and of which one is finely distributed in the other. The external phase is referred to as the continuous phase or dispersion medium, and the liquid distributed therein is referred to as the internal, discontinuous or disperse phase. 10 Cosmetic emulsions usually consist of an aqueous polar phase and a nonpolar oil phase. The term suspension on the other hand is taken to mean the distribution of very small, but not molecular particles of a solid in a liquid. Suspensions, like emulsions, are usually optically cloudy and tend to settle out under the influence of gravity. Emulsification processes are usually carried out in accordance with the following scheme: two substances which are insoluble in one another, namely fat and water, are mixed. In order to obtain a durable emulsion, 20 the fat and water phases must be comminuted mechanically to less than 10 pm and subsequently stabilised with the aid of an emulsifier. The oil and fat phase are normally initially introduced separately, warmed to 50 70 0 C and subsequently pre-emulsified. All water-soluble substances are located in the water phase, and all fat-soluble substances in the fat phase. 25 The pre-emulsion prepared by the hot/hot process (both phases are warmed separately to 50-70 0 C) is cooled to room temperature before addition of perfume oil and dye and is subsequently post-emulsified. Some cases of emulsion preparation can start from a water phase at 20 30 30 0 C. In this hot/cold process, cooling before addition of perfume oil and dye can be omitted. If the fat phase here is an oil which has low viscosity at room temperature, both phases can be initially introduced and emulsified at a temperature of 20-30 0 C (cold/cold process) (from W. Umbach, "Kosmetik" [Cosmetics], 35 Georg Thieme Verlag, Stuttgart, 1995).

-3 In the preparation of emulsions, suspensions and dispersions which are delivered to the end consumer, it is desirable to obtain products which are stable for an extended period, do not tend to separate out and in which at the same time the added active ingredients retain their activity. The 5 stability of mixtures is achieved in conventional products by the addition of additives, such as, for example, emulsifiers, surfactants or the like. In order to prevent decomposition of the contents and to hinder a decrease in the activity of active ingredients present, oxidation stabilisers, free radical scavengers, bactericides and other additives, for example, are 10 added. Various of these additives may result in irritation or allergies in the case of sensitive users. In order to stabilise active ingredients, it is in many cases not the active ingredient itself that is used, but instead one of its more stable derivatives, which then decomposes at the site of action and liberates the active 15 ingredient. This is of course afflicted with the problem that the derivative behaves differently to the actual active ingredient in any prior transport or metabolism processes which are necessary. A further problem in the preparation of the above-mentioned mixtures is 20 homogeneous mixing of the individual substances in each volume element of the mixture as a whole. In order to prepare cosmetic formulations, simple stirred vessels with various types of stirrer are frequently used. Depending on the stirrer type (for example anchor, propeller, inclined-blade, disc, EKATO multistage 25 impulse countercurrent stirrers or EKATO Mizer disc), different shear forces occur in the stirred vessels depending on the location in the stirred vessel. The same applies to the temperature distribution and energy input into the formulation, which means that shear forces, temperature and introduced energy are not "uniformly" distributed in the batch vessel, and 30 consequently the build-up of the resultant formulation is adversely affected. In concrete terms, this means that, for example, emulsions may form in which the emulsified phase has very different particle sizes, or the active-ingredient distribution in a prepared product is non-uniform. 35 The object of the present invention is therefore to provide a process which gives mixed products which have a homogeneous distribution of all -4 components in the mixture as a whole and at the same time have a homogeneous distribution of the particle or droplet size. A further object of the invention is to provide a process for the preparation of cosmetic or pharmaceutical formulations by means of which the use of emulsifiers, 5 surfactants, stabilisers, oxidation stabilisers, free-radical scavengers, bactericides and other additives can be restricted or by means of which, in the ideal case, their use can be omitted entirely. A further object of the invention is to provide a process by means of which cosmetic or pharma ceutical formulations can be prepared in very small amounts immediately 10 before their use. The object according to the invention is achieved by a process for the preparation of cosmetic or pharmaceutical formulations immediately before use, characterised in that two or more liquid components from 15 separate stock chambers are mixed with one another by passing them through a micromixer. In order to carry out the process according to the invention, two or more components in liquid form, if necessary after warming, from separate stock 20 chambers are passed through a micromixer for mixing. The mixing can take place by passing the components in liquid form, if necessary after warming, from separate stock chambers through a temperature-controlled micromixer and if necessary continuing stirring for 25 cooling. The process for the preparation of cosmetic or pharmaceutical formulations in the form of emulsions immediately before use can be carried out by passing one or more liquid component(s) with one or more 30 natural, synthetic or semi-synthetic oil(s) from separate stock chambers through a micromixer, during which they are mixed with one another. The object according to the invention is also achieved by a process for the preparation of cosmetic formulations in the form of emulsions immediately 35 before use, characterised in that a fat phase consisting of one or more natural, synthetic or semi-synthetic oil(s) and one or more fat(s) which is -5 (are) solid at room temperature, is liquefied in a stock chamber by warming, and this liquid fat phase is mixed with one or more liquid component(s) and optionally with a further oil phase by passing them through a micromixer. 5 In a particular embodiment of the process according to the invention, the components to be mixed are pumped from the stock chambers into a micromixer through connecting thin tubes, each of which terminates in a channel of the micromixer, and is forced through the channels of the 10 micromixer owing to the pressure which builds up due to the pumping, with intensive mixing and formation of an emulsion. It is also possible in accordance with the invention to convey the com ponents to be mixed from pressurised stock chambers through connecting 15 thin tubes, each of which terminates in a channel of a micromixer, to feed the components into the micromixer and to force them through the channels of the micromixer due to the pressure which builds up, with intensive mixing and formation of an emulsion. 20 The object according to the invention is furthermore achieved by a process for the preparation of liposome-containing formulations immediately before use by mixing one or more liquid component(s) with a component which contains liposome-forming contents from separate stock chambers with one another by passing them through a micromixer with formation of the 25 desired liposomes. This can be carried out after one or more of the com ponent(s) to be mixed has (have) been warmed before preparation of the formulation. This process can be carried out by pumping the components to be mixed from the stock chambers and feeding them into a micromixer through connecting thin tubes, each of which terminates in a channel of the 30 micromixer, and forcing them through the channels of the micromixer owing to the pressure which builds up due to the pumping, with intensive mixing and formation of a liposome-containing formulation. In particular, the components to be mixed can be conveyed from 35 pressurised stock chambers and fed into a micromixer through connecting thin tubes, each of which terminates in a channel of the micromixer. Owing -6 to the pressure prevailing in the stock chambers, an adequate pressure is built up in the micromixer to force the components through the channels with intensive mixing and formation of a liposome-containing formulation. 5 The present invention is also achieved by means of lotions or solution, emulsions, gels and creams which can be prepared by the process according to the invention. For certain formulations, uniform mixing, a constant temperature and 10 uniform input of energy even at the micro-level, are important. It has now been found that the use of micromixers enables the preparation of mixtures in the form of emulsions, suspensions and dispersions, lotions, solutions gels and creams in which all contents are uniformly distributed, even in extremely small volume parts. In contrast to a large-volume stirred 15 reactor, it is possible to prepare these mixtures under uniform temperature conditions, even at the micro-level, since no temperature gradient forms in the thin, optionally laminate-like channels, in particular if the micromixer has a temperature-controllable design. Furthermore, the input of energy is the same in each volume part, i.e. even in the smallest. It has also been 20 found that emulsions having a significantly more homogeneous droplet size distribution can be prepared than in a stirred vessel. Owing to the multiple shear conditions of the communicating channels in the micromixer, droplet sizes in the micro-range are inevitably specified, so that microemulsions are obtained, which could only be prepared in a very complex manner in a 25 stirred vessel. The use of a micromixer is therefore suitable for the preparation of very fine homogeneous formulations. Suitable for carrying out the process according to the invention are micromixers and associated connection and sealing systems which are 30 described in the patent applications DE 1 95 11 603, DE 1 97 46 583, DE 1 97 46 584, DE 19746585 and DE 1 98 54 096, and modifications thereof that are evident to the person skilled in the art. Suitable micro mixers may consist of suitable metallic, ceramic or polymeric materials or of silicon. 35 Problematic formulations in the W/O area are emulsions, in particular those having high contents of vegetable triglycerides. Emulsions without -7 stabilising waxes are frequently distinguished by inadequate long-term viscosity constancy, and O/W lotions are generally more difficult to stabilise than creams. These emulsions can therefore be prepared parti cularly well using micromixers. It is of particular advantage here than the 5 use of micromixers enables particularly small amounts to be prepared, which can advantageously be prepared in situ, i.e. directly before use. Microemulsions are thermodynamically stable if, owing to extremely low interfacial energy, they are formed spontaneously, i.e. without the supply 10 of external mechanical energy. The droplet diameters are significantly smaller than in the case of macroemulsions; they are in the range 10 30 nm (nanometers), i.e. below the wavelength of visible light. Micro emulsions are therefore colloidally disperse, optically transparent systems. According to POHLER, certain concentration ranges of the oil 15 and water phases and of the emulsifiers and auxiliaries must be observed for the formulation of microemulsions: Surfactants (usually nonionic surfactants) 15 - 40% Mineral oil or vegetable oil 5 - 25% 20 Polyalcohols 0- 20% Water 35-65% The use of micromixers for the preparation of microemulsions enables the 25 use of surfactants to be considerably reduced, enabling the toleration for particularly sensitive skin types to be significantly increased. Stable microemulsions can be prepared using as little as less than 10% by weight of surfactants. 30 The most important requirements of emulsification equipment are usually adequate and in particular variable emulsification power, sufficient shear or impact forces, fitting-out for uniform treatment of the batch, vacuum device, heating and cooling (14). These problems can be solved in a simple manner in accordance with the invention through the use of 35 suitable micromixers, which ensure specific input of energy in each volume element and in which intensive mixing takes place in the thin channels with exposure to intensive shear forces. The use of micromixers furthermore enables very small amounts of the 5 desired cosmetic or pharmaceutical formulations to be prepared immedi ately before use. This has the advantage that the addition of emulsifiers, suspension aids and dispersion aids in the form of surfactants and other additives, such as, for example, stabilisers, can be greatly restricted or their use can be omitted entirely. It is also possible in this way for active 10 ingredients or additives which are incompatible with one another in a form ulation over an extended period not to be mixed with one another until directly before use. Active ingredients which are only stable in a formulation in the form of a 15 derivative can be initially introduced as such in a separate formulation and not added to the remaining mixture until directly before use. This also enables the user to add various additives, as desired, to small amounts of a base mixture at various points in time. This may be of interest both for pharmaceutical and for cosmetic formulations if different active ingredients 20 are to be applied at different points in time. Different additives can be added to a cosmetic base formulation for the day than for the night. Additives for the day may be, for example, UV filters, while those for the night may be regenerating additives. 25 For better understanding and for illustration, examples are given below which fall within the scope of protection of the present invention, but are not suitable for restricting the invention to these examples. Example 1 30 Hand and nail cream Raw material INCI % WW A Paraffin (1) Mineral Oil 2.00 35 (Art. No. 107162) Arlamol HD (2) Isohexadecane 2.00 -9 Isopropyl palmitate (3) Isopropyl Palmitate 3.00 Soya oil (4) Glycine Soya 0.50 Mirasil DM 350 (5) Dimethicone 1.00 Lanette 0 (3) Cetearyl Alcohol 1.00 5 Span 60 (2) Sorbitan Stearate 1.50 Montanov 68 (6) Cetearyl Alcohol (and) Cetearyl Glucoside 4.00 (-) -(a-Bisabolol (1) Bisabolol 0.30 (Art. No.130170) 10 B Demin. water Aqua to 100 Glycerin, 87% (1) Glycerin 10.00 (Art. No.104091) D-Panthenol (7) Panthenol 0.50 (D+)-Biotin (1) Biotin 0.05 15 (Art. No.130220) (if desired) preservatives q.s. C Rhodicare S (5) Xanthan Gum 0.30 If desired: 20 D Perfume Bianca (8) Perfume 0.20 Preparation: 25 Phases A, B and C are each introduced separately into a stock container and heated to 75 0 C. The consequently liquid phases B and C are pumped out of the stock containers and passed through a micromixer held at 75 0 C and mixed. The mixture emerging from the micromixer is subsequently pumped with phase A through a micromixer held at 75 0 C and homogenised. The resultant emulsion is 30 collected in a stock container and cooled with stirring. At a temperature of about 35 0 C, the perfume can be added if desired. Notes: pH 2 5 -c value: 5.5 Viscosity: 43000 mPa.s (Brookfield RVT, spindle C, 5 rpm, Helipath) at 25 0 C 0.05% of propyl 4-hydroxybenzoate (Merck KGaA, Art. No. 130173), - 10 0.15% of methyl 4-hydroxybenzoate (Merck KGaA, Art. No. 13 0174), 0.30% of Germall 115 (ISP, Frechen) Procurement sources: 5 (1) Merck KGaA, Darmstadt (2) ICI Surfactants, Essen (3) Henkel KGaA, Dusseldorf (4) Gustav Hees, Stuttgart (5) Rhodia, Frankfurt 10 (6) Seppic, France (7) BASF, Ludwigshafen (8) HandR, Holzminden 15 20 25 30 35 - 11 Example 2 W/0 body-care milk (COLD PREPARATION) A. ARLACEL 780 5.0 % 5 Paraffin oil, low-viscosity 10.0 % Miglyol 812 4.0 % ARLAMOL HD 50% ARLAMOL E 1.0% 10 Perfume (if desired) q.s. B. Glycerin 2.5% ATLAS G-2330 1.5 % Mg SO 4 0.5% Demin. water 70.5% 15 Preservative (if desired) q.s. Preparation method: The two phases A and B are each introduced separately into a stock container. After mixing, which can be carried out either by 20 stirring or in small vessels by shaking, the phases are pumped out of the stock containers and passed jointly through a micro mixer, in which the phases are mixed intensively. The homogen eously mixed milk can be used directly. 25 Viscosity: 10 000 mPa s (Brookfield LVT Helipath, spindle C, 6 rpm, 1 min.) Procurement sources: 30 (1) ICI Surfactants Example 3 35 Sun-protection milk (W/S) (water in silicone) - 12 A Eusolex 2292 (Art. No. 5382) (1) 2.00 DC 1401 (2) 10.00 DC 3225 C (2) 10.00 Dow Corning 344 (2) 10.00 5 q.s. B Eusolex 232 (Art. No. 5372) (1) 2.00 Tris(hydroxymethyl) (1) 0.88 10 aminomethane (Art. No. 8386) Sodium chloride (Art. No. 6400) (1) 2.00 Glycerin (Art.-Nr. 4093) (1) 5.00 15 Preservative (if desired.) q.s. Water, demineralised to 100.00 20 Preparation: In order to prepare phase B, tris(hydroxymethyl)aminomethane for neutralisation of Eusolex 232 is dissolved in water in a stock vessel, and Eusolex 232 is added. After complete dissolution, the remaining raw 25 materials of phase B are added. The components of phase A are pre mixed in a second stock vessel. In order to prepare the sun-protection milk, the two phases are, for mixing, pumped jointly with the aid of a pump through a micromixer 30 connected via thin connecting tubes. Notes Viscosity 22,800 mPas (Brookfield RVT, spindle C, 10 rpm) at 25 'C Samples contain the following as preservatives: 35 0.05% of propyl 4-hydroxybenzoate (Merck Art. No. 7427) 0.17 % of methyl 4-hydroxybenzoate, sodium salt (Merck Art. No. 6756) - 13 Procurement sources: (1) E. Merck, Darmstadt (2) Dow Corning, Dusseldorf 5 Example 4 Transparent microemulsion Trade name INCI % by weight 10 Eumulgin B2 Ceteareth-20 19.5 Cetiol RE PEG-7 Glyceryl Cocoate 20.0 Uniphen P-23 Phenoxyethanol + Methyl-/ 15 Ethyl-/Propyl-/Butylparaben 0.3 Mineral oil Mineral Oil 5.0 Glycerin Glycerin 20.0 Water, demin.. Water 35.2 Preparation: 20 1. Eumulgin B2, Cetiol HE, Uniphen P-23 and the paraffin oil are intro duced into a stock vessel, melted with mixing and heated to about 95 0 C-105 0 C. 2. Water and the glycerin are combined and likewise heated to about 25 95 0 C-1 00*C. Increase the amount of water by 3%. 3. The water phase and the fat phase are pumped through a micromixer for intensive mixing. The resultant microemulsion gel stirs for cooling. Alternatively, it is possible to pass the microemulsion gel through a 30 further, cooled micromixer whose exit channels have a broader cross section, thus preventing blockage of the channels and suppressing the formation of air bubbles in the gel. At a temperature at which the microemulsion gel is still just pourable, it is 35 transferred into the primary packaging.

-14 Example 5 Sun-protection gel (emulsifier-free) SPF 3.21 UVA PF 2.5 (sun protection factor, Diffey Method) 5 % by weight A Eusolex 2292 (Art. No. 105382) (1) 1.000 Luvitol EHO (2) 9.000 Dow Corning 200 (100 cs) (3) 2.000 10 Antaron V-220 (4) 2.000 Jojoba oil (5) 5.000 DL-a-Tocopherol acetate (1) 0.500 (Art. No. 500952) 15 B Tris(hydroxymethyl)aminomethane (1) 0.700 (Art. No. 108386) Water, demineralised 14.300 C Pemulen TR-1 (6) 0.600 Preservative (if desired) (1) q.s. 20 Water, demineralised to 100. 000 D Aloe Vera Gel 1: 10 (7) 1.000 Preparation: 25 For phase C, homogeneously disperse the Pemulen TR-1 in water, add preservative and pre-swell. Introduce phase B into phase C with homogenisation. Dissolve phase A with heating and add slowly with homogenisation. Add phase D at 35 0 C and again homogenise. 30 Notes: Viscosity 67,000 mPas (Brookfield RVT, spindle C, 5 rpm) at 25 0 C PH25-c = 6.9 As preservative, 1.0% of phenoxyethanol (Merck Art. No. 807291) can be 35 added.

- 15 Procurement sources (1) Merck KGaA, Darmstadt (2) BASF, Ludwigshafen (3) Dow Corning, Dusseldorf (4) GAF, Frechen 5 (5) Henry Lamotte, Bremen (6) Goodrich, Neuss (7) Rahn, Maintal Example 6 In situ W/0/W super-moisturising cream 10 Composition: WAN A. 15 'Brij 721 2.0 Brij 72 3.0 Arlacel P135 0.5 Arlamol E 5.0 20 Arlamol HD 4.0 Vitamin E acetate 1.0 Laurex CS 1.0 Stearic acid 1.5 Mirasil DM 100 1.0 25 B 1.2-Propylene glycol 4.0 Allantoin 0.2 Urea 0.5 30 Water 74.4 C Germaben 11 1.0 35 - 16 D. (if desired) Perfume L94-5770 0.1 5 Preparation: 1. A and B are warmed to a temperature of 75 0 C in separate stock containers. 2. Before the emulsion is prepared, C is added to B. 10 3. The phases A and B/C are mixed intensively by pumping them through a micromixer held at 75 0 C. 4. The resultant emulsion is collected in a stock vessel. 15 5. If desired, D is added after cooling to a temperature below 35 0 C. 6. Further cooling to room temperature is carried out with gentle stirring. Notes: 20 Viscosity 43,000 mPa.s (Brookfield LVT T-bar spindle, E, rpm 6, 1 min.) Example 7 W/O/W face moisturiser (two-step preparation) 25 Composition: Primary emulsion W/O % W/W 30 A. Arlacel 1MO 3.3 Arlacel 2064 3.0 Arlamol HD 15.0 Arlamol' M812 14.0 35 B Water 63.7 Germaben 11 1.0 -17 Secondary emulsion W/O/W A. Primary emulsion W/O 50.0 B. 'Arlatone 2121 5.0 5 Water 44.1 Keltrol 0.4 C. Germaben Il 0.5 10 Preparation: Primary emulsion W/O 1. B is slowly added to A with vigorous stirring. 15 2. The resultant emulsion is homogenised for a further 5 minutes. Secondary emulsion W/0/W 1. The composition indicated under B with the exception of Keltrol is warmed to a temperature of 80 0 C. Keltrol is dispersed in the initially 20 introduced composition with stirring at constant temperature. The two separately prepared compositions A and B are mixed in a micromixer as described above. 2. C is added to the emulsion cooled to a temperature below 40 0 C. 25 3. The mixture is cooled to room temperature with gentle stirring.. Notes:: Viscosity 16,000 mPa.s (Brookfield LVT, T- ) spindle D, rpm 6, min.) 30 35

Claims

1. Process for the preparation of cosmetic or pharmaceutical formulations immediately before use, characterised in that two or more liquid com 5 ponents from separate stock chambers are mixed with one another by passing them through a micromixer.

2. Process for the preparation of cosmetic formulations, characterised in that, characterised in that two or more components in liquid form, if 10 necessary after warming, from separate stock chambers are passed through a micromixer for mixing.

3. Process according to Claims 1 to 2, characterised in that two or more components in liquid form, if necessary after warming, from separate 15 stock chambers are passed through a temperature-controlled micro mixer for mixing and subsequently stirred.

4. Process for the preparation of cosmetic formulations in the form of emulsions immediately before use, characterised in that one or more 20 liquid component(s) with one or more natural, synthetic or semi synthetic oil(s) from separate stock chambers are mixed with one another by passing them through a micromixer.

5. Process for the preparation of cosmetic formulations in the form of 25 emulsions immediately before use, characterised in that a fat phase consisting of one or more natural, synthetic or semi-synthetic oil(s) and one or more fat(s) which is (are) solid at room temperature, is liquefied in a stock chamber by warming, and this liquid fat phase is mixed with one or more liquid component(s) and, if desired, with a further oil phase 30 by passing them through a micromixer.

6. Process according to Claims 1 to 5, characterised in that the com ponents to be mixed are pumped from the stock chambers and fed into a micromixer through connecting thin tubes, each of which terminates 35 in a channel of the micromixer, and forced through the channels of the -19 micromixer owing to the pressure building up due to the pumping, with intensive mixing and formation of an emulsion.

7. Process according to Claims 1, 4 to 6, characterised in that the com 5 ponents to be mixed are pumped from the pressurised stock cham bers, fed into a micromixer through connecting thin tubes, each of which terminates in a channel of the micromixer, and forced through the channels of the micromixer owing to the pressure which builds up due to the pumping, with intensive mixing and formation of an 10 emulsion.

8. Process for the preparation of liposome-containing formulations immediately before use, characterised in that one or more liquid com ponent(s) with a component containing liposome-forming contents from 15 separate stock chambers are mixed with one another by passing them through a micromixer with formation of the desired liposomes.

9. Process for the preparation of liposome-containing formulations according to Claim 8, characterised in that one or more of the com 20 ponent(s) to be mixed is (are) warmed before preparation of the formulation.

10. Process according to Claims 8 to 9, characterised in that characterised in that the components to be mixed are pumped from the stock cham 25 bers and fed into a micromixer through connecting thin tubes, each of which terminates in a channel of the micromixer, and forced through the channels of the micromixer owing to the pressure which builds up due to the pumping, with intensive mixing and formation of a liposome containing formulation. 30

11. Process according to Claims 8 to 10, characterised in that the com ponents to be mixed are pumped from pressurised stock chambers and fed into a micromixer through connecting thin tubes, each of which terminates in a channel of the micromixer, and forced through the 35 channels of the micromixer owing to the pressure which builds up due - 20 to the pumping, with intensive mixing and formation of a liposome containing formulation.

12. Lotion or solution, prepared by a process according to Claims 1 to 11. 5

13. Emulsion, prepared by a process according to Claims 1 to 11.

14. Gel, prepared by a process according to Claims 1 to 11. 10 15. Cream, prepared by a process according to Claims 1 to 11.

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