Claims
- 1. Process for the preparation of fineparticled, stable, pharmaceutical or cosmetic dispersions consisting of an aqueous phase and an organic oily phase which is insoluble or not completely soluble in water, characterized in that a pre-emulsion is pumped through a jet disperser under a pressure of 2 to 50 bar, said jet disperser consisting of one or more jets, which are designed as capillary bores with a diameter of 0.5 to 0.8 mm and have a length to diameter ratio of 1.5 to 2 in the course of which all the pressure energy is consumed in the dispersing zone and the dispersion leaves the dispersing zone as a non-directional stream.
- 2. A process according to claim 1, wherein the organic phase contains a mixture of glycerol esters or fatty acid esters and/or liquid, semi-solid and solid hydrocarbons, as well as polyhydric alcohols, non-ionic emulsifiers and fat-soluble pharmaceutical or cosmetic active compounds, and the aqueous phase contains an aqueous solution of glycerol, glycols, low-molecular monohydric alcohols and cosmetic or pharmaceutical active compounds, with the addition of substances which increase the viscosity and preservatives.
- 3. A process according to claim 1, wherein the pre-emulsion is pumped through the jet disperser under a pressure of 10 to 50 bar.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 3230289 |
Aug 1982 |
DEX |
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Parent Case Info
This is a continuation of application Ser. No. 324,985, filed Mar. 15, 1989 now U.S. Pat. No. 4,996,004 which is a continuation of application Ser. No. 518,902 filed Aug. 1, 1983 now abandoned.
The invention relates to a process for the preparation of fine-particled, stable, pharmaceutical or cosmetic dispersions consisting of an aqueous phase and an organic phase which is insoluble or not completely soluble in water (oily phase), in which a pre-emulsion is first prepared from the two phases by known emulsifying methods and is then further processed to the end product. The invention furthermore relates to apparatus for carrying out the process.
Pharmaceutical or cosmetic emulsions are usually prepared by combining, at a temperature of 60.degree. to 80.degree. C., the molten organic phase (oily phase) and the entire aqueous phase, which has been brought to the same temperature, in a stirred kettle and, in the case of ointments and creams, cooling the mixture to room temperature in an ointment reactor with stirring and homogenising tools and thereby homogenising it. In the case of emulsions which are capable of flowing, the crude emulsion thus obtained is pre-emulsified, cooled to 20.degree. to 40.degree. C. in a jacketed or flow-through cooler and then very finely dispersed with a high-pressure homogeniser. A disadvantage in this type of preparation of an emulsion which is capable of flowing is that the entire batch must first be heated up and then cooled again, after pre-emulsification, in order to bring the entire emulsion to the desired fineness with frequently only a small amount of disperse oily phase by means of high-pressure homogenisers. High-pressure homogenisers require a very high operating pressure in the order of size of 200 bar, which can only be produced with relatively expensive multistage high-pressure piston pumps of high power. Moreover, the temperature programme described above, necessitated by the technology, gives rise to a high energy consumption.
A further disadvantage is that high-molecular organic compounds may be destroyed by the high shearing forces in the high-pressure homogeniser, so that damage to the product occurs.
Expensive ointment reactors (heavy machine columns, vacuum devices, complicated shaft packing and the like) in which completely undefined preparation conditions prevail as a result of simultaneous stirring, homogenising and cooling (for example each volume element of the product will pass through the shearing gap of the homogeniser only on a statistical average basis) have hitherto been used for the preparation of ointment and cream products. Moreover, poor heat transfer gives rise to long cooling times.
The invention is based on the object of improving the economics of the known processes. This is to be understood as meaning that the aim is also an advantageous energy balance, together with the least possible expenditure on apparatus (reduction of the capital and operating costs). As a peripheral condition, it should be ensured that no damage occurs to the product (shearing forces too high) and that the properties of the particles (average particle size and particle size distribution) are the same as in the known processes.
According to the invention, this object is achieved, starting from the process described above, by a process in which the pre-emulsion prepared by known emulsifying methods is passed to a jet disperser in which homogenisation and fine dispersion characteristic for the end product is carried out. "Jet disperser" here is understood as meaning a pressure release jet in which the pressure energy available is dissipated in a dispersing zone in the smallest possible volume and a high dispersing efficiency, based on the volume, is achieved.
The process according to the invention is advantageously combined with a phase inversion process. In the phase inversion process, to prepare the pre-emulsion, the oily phase is first taken, as the external phase, and the aqueous phase is emulsified therein, as the internal phase. Thus, in contrast to the end product, the aqueous phase forms the internal (disperse) phase and the oily phase forms the external (continuous) phase in the pre-emulsion. The pre-emulsion thus prepared is then pumped through the jet disperser in the subsequent process step, the temperature, proportions of the two phases and pressure in the jet disperser being adjusted so that phase inversion of the emulsion takes place in the jet disperser at the same time as homogenisation and fine dispersion. On passing through the jet disperser, the aqueous phase is thus converted into the external phase and the oily phase is converted into the internal phase. The phase inversion temperature appropriate for certain proportions can be determined empirically without problems.
Use of the phase inversion process in combination with the jet disperser leads to a very simple dispersing process. For example, if, for homogenisation by the standard technique, a homogenising pressure of 200 bar were required using a high-pressure homogeniser and 40 to 50 bar were required using a jet disperser, an operating pressure in the range of only 2 to 50 bar, preferably 10 to 50 bar, which can be produced even with relatively simple and inexpensive pumps, is sufficient for the combination of jet dispersion and the phase inversion process.
A preferred embodiment of the invention comprises carrying out the phase inversion at a concentration of 50 to 70% by weight of oily phase (corresponding to 50 to 30% by weight of aqueous phase). This means that a highly concentrated emulsion is obtained on jet dispersion and is later diluted to the desired end concentration. Dilution is effected by adding cold aqueous phase, so that cooling takes place at the same time. Since the process has to be carried out with only a fraction of the total amount of emulsion, a high space/time yield is achieved, together with an advantageous energy balance. This means that it is possible to prepare either the same amount, in comparison with the processes used earlier, with a smaller kettle Volume, or a considerably greater amount of product, with a correspondingly enlarged diluter kettle capacity, in one batch. Cosmetic and pharmaceutical dispersions (see examples 1 to 4) are generally composed of the following base components:
1. The aqueous phase consists of an aqueous solution of glycerol, glycol, cosmetic or pharmaceutical active compounds, additives which increase the viscosity and preservatives.
2. The organic oily phase which is insoluble or not completely soluble in water consists of glycerol esters or fatty acid esters and/or liquid or semi-solid hydrocarbons, polyhydric alcohols, non-ionic emulsifiers and fat-soluble pharmaceutical or cosmetic active compounds.
In the pre-emulsion, the aqueous phase forms the internal phase and the oily phase the external phase, whilst in the finished end product the oily phase is finely dispersed as an internal phase in the aqueous phase.
The process according to the invention is carried out with two emulsifying apparatuses connected in series. The second emulsifying apparatus is a jet disperser, which operates under technologically optimum conditions. It consists of one or more jets, which are designed as capillary bores with a diameter of 0.3 to 1 mm, preferably 0.5 to 0.8 mm, and have a length to diameter ratio of 1 to 4, preferably of 1.5 to 2. With these dimensions, the volume of the dispersing zone is only 0.1 mm.sup.3 to 1 mm.sup.3. It has been found that almost all the pump energy is used up in the dispersing zone and the dispersion leaves the dispersing zone as a non-directional stream.
The jets are arranged either so that the issuing stream of emulsion hits a solid wall or the streams of emulsion collide with one another. In the latter embodiment, the kinetic energies still present after the streams have issued from the jets are used up by the streams colliding.
The essential and surprising advantage of the process according to the invention is that an improved space/time yield is achieved with a simplified apparatus. The fact that the same particle fineness as with the high-pressure homogenisers used earlier can be achieved with the jet disperser even with a substantially lower pressure and as a result less expensive pumps is of importance. Moreover, the process is not harmful to the product, since the high-molecular constituents in the oily phase and the aqueous phase are exposed to lower shearing forces in the jet disperser. In contrast to earlier processes, the energetic process conditions are strictly defined in the preparation of ointments and creams. The pre-emulsion completely is forced to flow through a dispersion zone of uniform energy dissipation density. In particular, a very narrow particle size distribution spectrum is produced in the jet disperser. Transfer of the model from the laboratory scale to the production scale is thus entirely without problems. In the text which follows, the invention is described in more detail with the aid of embodiment examples and drawings. In the figures:
US Referenced Citations (9)
Foreign Referenced Citations (1)
| Number |
Date |
Country |
| 764918 |
Jan 1957 |
GBX |
Non-Patent Literature Citations (1)
| Entry |
| CRC Handbook of Chemistry and Physics, 62nd Edition, 1981-1982, Weast and Astle, pp. F-115, F-116 and F-119. |
Continuations (2)
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Number |
Date |
Country |
| Parent |
07324985 |
Mar 1989 |
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| Parent |
518902 |
Aug 1983 |
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Patent Grant
5116536
