CA2182786C - Process for the production of particles or powders - Google Patents
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- CA2182786C CA2182786C CA002182786A CA2182786A CA2182786C CA 2182786 C CA2182786 C CA 2182786C CA 002182786 A CA002182786 A CA 002182786A CA 2182786 A CA2182786 A CA 2182786A CA 2182786 C CA2182786 C CA 2182786C
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
- B01J2/02—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops
- B01J2/04—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic by dividing the liquid material into drops, e.g. by spraying, and solidifying the drops in a gaseous medium
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
Abstract
In a novel process for the production of parti-cles or powders, a substance or mixture of substances to be treated is provided in a pressure vessel. A compress-ible fluid is dissolved under pressure in the substance or mixture of substances provided, and the resulting solution is then decompressed so that particles form during the decompression. The particles which have formed are removed from the stream of decompressed compressible fluid.
Description
~~.8~7~~
Process for the production of particles or powders The invention relates to a process for the production of particles or powders.
Prior art The particles and particle size distributions of solid substances which result in industrial chemical processes are generally not those required or necessary for further use of these substances. Such substances are therefore frequently comminuted or recrystallized.
Conventional processes for changing particles sizes and distributions are crushing/grinding, atomization/spray crystallization, freeze drying, sublimation, recrystallization from solutions. The use of said processes is associated with various technical disadvantages. In the mechanical processes there is sometimes considerable heating of the treated substances, which may lead to decomposition of the constituents in the case of thermally unstable substances or mixtures of substances. The thermal processes such as. for example, sublimation or freeze drying can be applied to only a few substances. In crystallization processes there is use of solvents which can be removed from the solids only with difficulty and often result as waste.
It is also known to employ compressible fluids, for example near-critcal or supercritical fluids, for producing particles or powders. Three examples thereof are indicated below:
1. Crystallization from supercritical solutions Compared with conventional solvent crystallization, this process is particularly advantageous when LcW volatile, thermally sensitive substances are to be crystallized. Fluids with a critical temperature in the region of ambient temperature are employed as non-toxic solvents and as an interesting alternative to classical organic solvents /1/.
Process for the production of particles or powders The invention relates to a process for the production of particles or powders.
Prior art The particles and particle size distributions of solid substances which result in industrial chemical processes are generally not those required or necessary for further use of these substances. Such substances are therefore frequently comminuted or recrystallized.
Conventional processes for changing particles sizes and distributions are crushing/grinding, atomization/spray crystallization, freeze drying, sublimation, recrystallization from solutions. The use of said processes is associated with various technical disadvantages. In the mechanical processes there is sometimes considerable heating of the treated substances, which may lead to decomposition of the constituents in the case of thermally unstable substances or mixtures of substances. The thermal processes such as. for example, sublimation or freeze drying can be applied to only a few substances. In crystallization processes there is use of solvents which can be removed from the solids only with difficulty and often result as waste.
It is also known to employ compressible fluids, for example near-critcal or supercritical fluids, for producing particles or powders. Three examples thereof are indicated below:
1. Crystallization from supercritical solutions Compared with conventional solvent crystallization, this process is particularly advantageous when LcW volatile, thermally sensitive substances are to be crystallized. Fluids with a critical temperature in the region of ambient temperature are employed as non-toxic solvents and as an interesting alternative to classical organic solvents /1/.
2~ ~2"~8~
In the conventional cooling crystallization which is carried out batchwise, a saturated solution is cooled, starting from a high temperature at which the solvent has good dissolving capacity, along an optimal cooling curve to the final temperature. The dissolving capacity is thus reduced and the dissolved substance precipitates at least partially. Optimization of the cooling curve is necessary in order to adjust to a supersaturation which is as constant as possible and to a constant crystal growth.
In the case where the solvent is a supercritical fluid in which the substance to be crystallized is dissolved, it is likewise necessary to optimize supersaturation and crystal growth. In this case, in distinction from conventional crystallization, the pressure prevailing in the crystallization container is another parameter available for influencing crystal formation. Typical crystallization times are between 30 min and several hours. After decompression of the container contents, the crystals are in the form of a solvent-free solid.
2. RESS process (Raid Expansion of a Supercritical Solution) In the RESS process. a solid is dissolved in a supercritical fluid under pressure, and the supercritical solution forated in this way is then decompressed to a lower pressure, preferably to atmospheric pressure. The dissolving capacity of the supercritical fluid is very rapidly reduced thereby, and the substance to be crystallized precipitates as solid. The applicability of this concept has been shows for some classes of substances. These include polymers /2/, dyes /3/, pharmaceuticals /4/ and inorganic substances /5/. The supersaturation and the rate of nucleation are influenced by varying the process conditions. It is possible in this way to obtain particles whose size, size distribution and morphology differ very greatly from the solid starting material. It is characteristic of the process that the 2~.~2~°~
In the conventional cooling crystallization which is carried out batchwise, a saturated solution is cooled, starting from a high temperature at which the solvent has good dissolving capacity, along an optimal cooling curve to the final temperature. The dissolving capacity is thus reduced and the dissolved substance precipitates at least partially. Optimization of the cooling curve is necessary in order to adjust to a supersaturation which is as constant as possible and to a constant crystal growth.
In the case where the solvent is a supercritical fluid in which the substance to be crystallized is dissolved, it is likewise necessary to optimize supersaturation and crystal growth. In this case, in distinction from conventional crystallization, the pressure prevailing in the crystallization container is another parameter available for influencing crystal formation. Typical crystallization times are between 30 min and several hours. After decompression of the container contents, the crystals are in the form of a solvent-free solid.
2. RESS process (Raid Expansion of a Supercritical Solution) In the RESS process. a solid is dissolved in a supercritical fluid under pressure, and the supercritical solution forated in this way is then decompressed to a lower pressure, preferably to atmospheric pressure. The dissolving capacity of the supercritical fluid is very rapidly reduced thereby, and the substance to be crystallized precipitates as solid. The applicability of this concept has been shows for some classes of substances. These include polymers /2/, dyes /3/, pharmaceuticals /4/ and inorganic substances /5/. The supersaturation and the rate of nucleation are influenced by varying the process conditions. It is possible in this way to obtain particles whose size, size distribution and morphology differ very greatly from the solid starting material. It is characteristic of the process that the 2~.~2~°~
supersaturation reached, by reason of the cooling and the large reduction in density of the supercritical fluid on decompression, is extremely high.
3. GASR process (Gas Antisolvent Recrystallization) This technique is preferably used for substances which are insoluble in supercritical media. In this method, the solubility of a gas under pressure in an organic solvent is utilized in order to reduce the dissolving capacity of this organic solvent for substances dissolved therein. Addition of the gas induces precipitation. It is also possible in this process, by varying the pressure, temperature and type of gas, to vary the properties of the particle populations in wide limits. A considerable advantage of the high-pressure process - the freedom from solvent - is, however, dispensed with in the GASR process.
The known uses of supercritical fluids for producing solids have various disadvantages. The crystallization processes (crystallization from supercritical fluids and gas antisolvent crystallization) can be carried out only batchwise and require long cooling or pressure-changing times (several hours in some cases). After the crystallization phase is complete, the autoclave contents must be decompressed in order to be-able to discharge the solid products. In the case of the GASI~process, the product results after the decompression aad the removal of gas associated therewith in suspended form in the solvent or as moist cake of solid. The solid must be removed and dried by suitable measures. Very high pressures aad large amounts of gas are necessary for crystallization from supercritical fluids because the relevant substances often have only low solubility in supercritical fluids. Tavana and Randolph /1/ describe, for example, the crystallization of benzoic acid from a solution in carbon dioxide. Under a pressure of 282.8 bar and at a temperature of 55°C, the solubility of benzoic acid in carbon dioxide is 2~ by weight. On the assumption ~~~~~U~
3. GASR process (Gas Antisolvent Recrystallization) This technique is preferably used for substances which are insoluble in supercritical media. In this method, the solubility of a gas under pressure in an organic solvent is utilized in order to reduce the dissolving capacity of this organic solvent for substances dissolved therein. Addition of the gas induces precipitation. It is also possible in this process, by varying the pressure, temperature and type of gas, to vary the properties of the particle populations in wide limits. A considerable advantage of the high-pressure process - the freedom from solvent - is, however, dispensed with in the GASR process.
The known uses of supercritical fluids for producing solids have various disadvantages. The crystallization processes (crystallization from supercritical fluids and gas antisolvent crystallization) can be carried out only batchwise and require long cooling or pressure-changing times (several hours in some cases). After the crystallization phase is complete, the autoclave contents must be decompressed in order to be-able to discharge the solid products. In the case of the GASI~process, the product results after the decompression aad the removal of gas associated therewith in suspended form in the solvent or as moist cake of solid. The solid must be removed and dried by suitable measures. Very high pressures aad large amounts of gas are necessary for crystallization from supercritical fluids because the relevant substances often have only low solubility in supercritical fluids. Tavana and Randolph /1/ describe, for example, the crystallization of benzoic acid from a solution in carbon dioxide. Under a pressure of 282.8 bar and at a temperature of 55°C, the solubility of benzoic acid in carbon dioxide is 2~ by weight. On the assumption ~~~~~U~
that all the benzoic acid is obtained as crystals, it is accordingly necessary to cool 49 kg of gas to the final crystallization temperature of 35°C for 1 kg of product.
In addition to the thermal energy requirement, considerable amounts of energy are needed for mechanical recompression of the large amounts of gas.
Similar factors also apply to the RESS process.
In this case too, very high pressures of, in some cases, above 600 bar /5/ and large excesses of gas are necessary to dissolve solids in the supercritical fluid. Processes requiring several hundred kilograms of gas to obtain 1 kg of powder are described.
It is likewise known from gas extraction that supercritical media have a poor dissolving capacity for very many substances. Hence very high pressures and large amounts of solvent are necessary both in gas extraction and in the processes described above for producing particles.
Description of the invention The invention is based on the object of providing a process which avoids the abovementioned disadvantages of the classical processes and of the high-pressure processes.
This object is achieved according to the invention by a process which comprises the steps stated in claim 1. Preferred embodiments and further developments of the process according to the invention are indicated in the dependent claims.
The process according to the invention is based on the surprising finding that it is unnecessary to start from supercritical solutions to produce particles. On the contrary, it is entirely sufficient to dissolve gases or, in general, compressible fluids in the substance to be treated. The solution produced in this way, which is preferably saturated with compressible fluid, is rapidly decompressed in a suitable decompression apparatus. When the compressible fluid used is a gas, this escapes on decompression and brings about a cooling which is so great that the temperature falls below the solidification point of the substance to be treated. The substance precipitates in fine-particle form and is removed from the stream of gas by suitable processes (for example sedimentation, cylone, filtration, electrofiltration) and, if required, fractionated. Since the procedure is as just described, the process according to the invention is also referred to hereinafter as the PGSS process (Particles from Gas Saturated Solutions).
The substance to be treated can be either a solid or a liquid under ambient conditions. If the substance to be treated or the mixture of substances to be treated is in the form of a solid, a liquid solution under pressure is produced by dissolving the compressible fluid. The mass ratio between the compressible fluid and the substance to be treated is in this case between 0.1:1 and 4:1 and is thus 2 to 3 orders of magnitude less than in the other high-pressure process techniques for producing solids.
The solubility of gases in liquids is considerably greater than that of liquids/solids in gases. Thus, the solubility of stearic acid in ethane at a temperature of 80°C and under a pressure of 37 bar is 0.002% by weight. However, the solubility of ethane in stearic acid under the same conditions of pressure and temperature is as much as 5.62% by weight. On -decompression of the gas-containing liquid solution of, for 'example, ethane in stearic acid in a suitable apparatus, for example a coa~ercially obtainable high-pressure nozzle, the compressed fluid, in this case ethane, is returned to the gaseous state. It has now been found, surprisingly and unpredictably for the skilled worker, that .the cooling is so great, despite the unusually low gas content, that the temperature falls below the solidification point of the substance to be treated downstream of the decompression apparatus. The substance to be treated therefore precipitates as a fine-particle solid. For the solidification point to be reached it is necessary to comply with certain outline ~~~2 ~~6 conditions concerning the temperatures at which the compressible fluid is dissolved. The guideline is that the temperature before decompression should, in the case of substances or mixtures of substances which have a clearly defined melting point, be in the region of ~50 R, preferably ~20 R, above or below the melting point under atmospheric pressure. The process according to the invention results in solutions of a substance or of a mixture of substances even at temperatures below the melting point of this substance or mixture of substances under standard conditions, that is say under atmospheric pressure. It is thus evident that the melting point of a substance or of a mixture of substances is reduced by dissolving a compressible fluid under pressure. Thus, for example, it has been found that the melting point of glycerol 1-stearic ester, which is at 75°C under atmospheric pressure, declines to 58°C in a carbon dioxide atmosphere of 150 bar. Under a propane atmosphere, a melting point of 58°C is reached under a pressure of only 20 bar.
This fact is of particular importance in the treatment of substances which decompose even before reaching the melting point. It is possible according to the invention, by selecting a suitable compressible fluid, to achieve liquid solutions at temperatures which are distinctly below the decomposition point.
In another embodiment of the process according to the 'invention. the melting point of a substance is reduced by adding an incompressible auxiliary. The incompressible auxiliary is chosen in this case so that it forms a low-melting eutectic with the substance to be sprayed. Then a compressible fluid is dissolved, in the manner described above, in the eutectic mixture formed in this way and the resulting liquid solution is rapidly decompressed. The eutectic mixture solidifies due to the cooling after decompression.
Suitable compressible fluids are a whole series of substances. In a preferred embodiment,. carbon dioxide, short-chain alkanes, dinitrogen monoxide, nitrogen alone ~182'~86 or in mixtures are employed. However, in principle, it is possible to use the vapor phase of any of the substances mentioned in Table 1, and mixtures of these substances, as compressible fluid.
Table 1 Compound Boiling Critical Critical Critical point temperaturepressure density [CJ (CJ Ibar1 fkg/m'1 CO= -78.5 31.. 72.9 0.448 NH3 -33.35 132.4 112.5 0.235 HZO 100.00 374.15 218.3 0.315 l~ N,0 -88.56 36.5 71.7 0.45 CH, -164.00 -82.1 45.8 0.2 Ethane -88.63 32.28 48.1 0.203 Ethylene -103.7 9.21 49.7 0.218 Propane -42.1 96.67 41.9 0.217 1 Propylene -47.4 91.9 45.4 S
n-Butane -0.5 152.0 37.5 i-Butana -11.7 134.7 35.9 n-Peatana 36.1 196.6 33.3 0.232 Benzene 80.1 288.9 48.3 0.302 Methanol 64.7 240.5 78.9 0.272 Ethahol 78.5 243.0 63.0 0.276 Iaopropanol 82.5 235.3 47.0 0.273 Isobutaaol 108.0 275.0 42.4 0.272 Chlorotrifluoromethane-31.2 28.0 38.7 0.579 2 Monofluoromethane 78.9 44.6 58.0 0.3 Toluene 110.6 320.0 40.6 0.292 Pyridine 115.5 347.0 55.6 0.312 Cyclohexane 80.74 280.0 40.2 0.273 Cyclohexanol 155.65 391.0 25.8 0.254 3 o-xylene 149.4 357.0 35.0 0.284 ~ CA 02182786 2003-04-22 The PGSS process provided according to the invention is a particularly interesting and universal alternative to conventional processes for producing particles. The main advantages compared with conventional processes are:
~ considerably lower pressures than in crystallization from supercritical solutions or in the RESS process ~ excellent flexibility and considerably smaller gas requirement because of the good solubility of the compressible fluids in liquids; 0.1 - 1 kg of gas per kilogram of solid produced is typical, and this value is unusually low by comparison with classical processes for producing solids, for example spray drying, spray crystallization and low-temperature grinding, since gases are required in the form of drying media or as cooling medium in the processes just mentioned. Typical figures for gas usage are therefore between 2 and 20 kg of gas/kg of solid in those cases.
~ possibility of circulating the gas after the solids have separated out ~ no waste streams or residual solvents to be disposed of ~ the solid particles produced are free of solvent ~ the PGSS process can be applied successfully to products which cannot be powdered by other processes (for example waxes and resins or else polymeric compounds with unusual rheological properties) ~ the process is suitable for thermally sensitive substances because low temperatures can be used ~ the process is also suitable for powdering mixtures of substances; the temperature at which the gas dissolves can be influenced in very wide limits by suitable selection of incompressible auxiliaries ~ dust explosions are avoided when inert gases are used as compressible media.
In accordance with another aspect of the present invention, there is provided a process for the production 8a of particles or powders, in particular of solid particles, having the steps:
provision of a pressure vessel which contains a substance or mixture of substances to be treated, dissolution of a compressible fluid under pressure in the substance or mixture of substances provided, until a solution forms, decompression of the resulting solution by means of a decompression apparatus in such a way that the temperature fails below the solidification point of the substance or mixture of substances downstream of the decompression apparatus, and formation of particles takes place, and removal of the particles which have formed from the stream of decompressed compressible fluid.
Preferred examples of the process according to the invention are explained in detail hereinafter, also referring to the appended drawings, which show:
_ g _ Fig. 1 a diagrammatic representation of an apparatus suitable for carrying out the process according to the invention, and.
Fig. 2 a particle size distribution obtained in one test (see Example 4).
An apparatus suitable for carrying out the process according to the invention is explained in detail by means of Fig. 1. A substance to be treated or a mixture of substances to be treated is melted in a feed vessel A. An autoclave C (V=5 liter, pm"~=400 bar, T~=250°C) is evacuated before starting the test.
Subsequently, the molten substance or mixture of substances is sucked in. The compressible fluid is conveyed into the autoclave up to the required pressure using a high-pressure pump H which is operated by compressed air in this case. The pressure is measured by an analog manometer (0-600 bar).
A high-pressure circulating pump E is used to draw off the liquid phase at the base of the autoclave and convey it to the top of the autoclave C. The liquid phase circulation intensifies material exchange between the liquid and gaseous phase; the rate of dissolution of the gas in the liquid is increased. During the dissolution of the gas. the pressure and temperature are manually corrected where appropriate via control loops.
The autoclave is provided with sampling devices with whose aid it is possible to measure the gas content in the liquid phase. When the required gas content is reached, the spray process is initiated. To do this, the gas-containing liquid is passed via a thermostated line to the top of a spray tower F which has previously been evacuated by means of a vacuum pump and/or flushed with inert gas (for example COz, Nz), in order to preclude the danger of dust explosions with atmospheric oxygen. The gas-containing liquid is decompressed through a suitable decompression apparatus, for example a high-pressure - nozzle. It is also possible alternatively to employ other decompression elements (manual valve,. control valve, capillaries, orifices etc.). In another embodiment it is X18? r~~
-possible for an additional gas stream to be metered in directly upstream of the nozzle or in the nozzle. Smaller particle sizes can be obtained in this way.
The mass flow of gas-containing liquid fed to the 5 spray tower can be measured by a mass flow apparatus according to the Coriolis principle. In order to avoid a fall in pressure in the autoclave during the spray process, fresh, preheated gas is metered into the top of the autoclave by the high-pressure pump B.
10 On decompression of the solution containing the compressed fluid, the compressible fluid is converted into the gaseous state. This results in cooling of the mixture of compressible fluid and substance or mixture of substances to be powdered, and in precipitation of solid.
The temperature and the temperature distribution in the spray tower can be measured with displaceable thermoelements. The spray tower has dimensions such that preferentially particles with an equivalent diameter of 10 N.m are deposited by sedimentation. The particles are collected in a discharge vessel or can be continuously discharged using a suitable apparatus (airlock, screw, fluidized bed with overflow inter alia). The spray tower can be provided with viewing windows to inspect the spray process.
The gas stream from which the larger particles have been removed leaves the spray tower at the upper end and is fed to a cyclone. The cyclone has dimensions such that preferentially particles with a size above 1 ~.m are deposited. The particles are collected in a discharge vessel fixed on the lower end of the cyclone.
To remove particles below 1 Vim, the gas stream leaving the cyclone is passed through an electric field in an electrostatic precipitator. The supply voltage is 20 kV. The particles are deposited on a central wire and shaken off at regular intervals. It is also possible. as an alternative to the electrostatic precipitator, to employ other fine filters (for example fabric filters and the like).
The residual gas is passed out of the system ~~8~ ~~~
through a volume flow gauge and can be recompressed and returned to the autoclave. The gas can also, where appropriate, be continuously extracted from the system by means of a blower.
The system and mode of operation described comprise one possible embodiment of the process. Refer-ence has been made to some other embodiments and modifi-cations. Other industrially relevant alternatives com-prise in particular the generation of the required solution from compressible fluid and substance or mixture of substances to be treated. It is possible in this case to employ, in place of the autoclave C, for example a static mixer in which the material exchange between liquid and compressible fluid is particularly efficient.
The process can be operated continuously when a static a~,xer is used.
Examples Example 1:
Glyceride mixtures from palm kernel oil which are starting materials for producing emulsifiers and deter gents are sprayed using propane. The melting point of the product, which consists of 60~ monoglycerides, 37~
diglycerides and 2~ triglycerides, and 1% free fatty acids, is 44°C. The product is saturated with propane in an autoclave at a -emperature of 45°C and under a pres-sure'of 260 bar and sprayed through a nozzle. The height of free fall after emerging from the nozzle is 0.25 m. A
fine-particle powder with an average particle size of 10.5 N.m is obtained. The temperature of the powder i~ediately after spraying is 0°C. The apparent density of the powder is 80 g/1.
Example 2:
The mixture from Example 1 forms a liquid solu tion with propane under a pressure of 230 bar and at a temperature of 37°C (which is 7°C below the melting point under atmospheric conditions). The propane-containing ~1~~ ~8 (about 35~ by weight) glycerides are sprayed through a nozzle. The height of fall after emerging from the nozzle is 1.0 m. The average particle size is 9.5 ~.m. The temperature after decompression is -3°C. The apparent density of the resulting powder is 55 g/1.
Example 3:
Propane is dissolved in the glyceride mixture from Example 1 at a temperature of 47°C and under a pressure of 20 bar. The propane content is 22~ by weight.
The liquid solution formed in this way is sprayed through a nozzle. The height of fall after emerging from the nozzle is 1.0 m. The average particle size is 25 Vim. The temperature after decompression is 30°C.
Example 4:
Monoglycerides of stearic acid are employed on a large scale as physiologically acceptable, highly effec-tive emulsifier in food technology. A glycerol 1-stearic ester with a melting point of 75°C and a purity of 99~ by weight is sprayed. Carbon dioxide is dissolved under a pressure of 80 bar in the monostearate at a temperature of 85°C. The mass ratio between carbon dioxide and monostearate is 0.18:1. After spraying through a nozzle (height of fall about 1.8 m), a fine-particle white powder with an average particle size of 12.8 ~m and an apparent density of 39 g/1 is obtained. A powder with an average particle size of 7.8 Ecm is drawn off from the cyclone. A few mg of particles with a particle size < 1 ~Cm are deposited in the electrostatic precipitator.
The particle size and particle size distribution of the powder drawn off from the spray tower are shown in Fig.
2, and the numerical values are shown in Tab. 2.
~~~~~8 Table 2 Diameter 0.7 0.9 1.0 1.4 1.7 2.0 2.6 3.2 4.0 S.0 Total % contents5.2 5.9 6.2 7.5 8.7 10.213.015.417.8 20.1 by mass Diameter 6.0 8.0 10.012.0 15.018.023.030.036.0 95.0 ~m Total % coatents22.2 26.028.130.3 36.548.273.497.1100 100 by mass 1 Diameter 56.0 70.090.010 35 65 210 60 320 400 ~m Total % conteats100 100 00 00 00 00 100 00 100 100 by mass Example 5:
Citric acid has a melting point of 156°C under atmospheric pressure. Citric acid is mixed in the mass ratio 1:3 with polyethylene glycol having an average molecular weight of 1500 g/mol and a melting range of 44-48°C. The mixture produced in this way melts in a temperature range between +2 and +5°C, that is to say the two substances form a eutectic with a melting point below the melting points of the two pure substances. Carbon dioxide is dissolved under a pressure of 200 bar in the mixture of citric acid and polyethylene glycol in a pressure vessel at a temperature of 20°C. The gas-con- -taining solution formed in this way is decompressed in a nozzle. A coprecipitate of citric acid and polyethylene glycol in powder form with a temperature of -5°C results.
The average particle size is 300 Vim. It is accordingly possible, by adding a suitable auxiliary, to reduce the temperature at which the required product (in this case citric acid) is to be saturated with gas considerably below the melting point of the product under atmospheric conditions.
Example 6:
Carbon dioxide is dissolved under a pressure of 200 bar in a polyether with an average molecular weight ~1~2'~~
of 3500 g/mol and a melting point of 42°C at a tempera-ture of 45°C. The gas-containing solution is decompressed through a manually operated metering valve into a col-lecting vessel. The height of the fall to the bottom of the collecting vessel is about 0.4 m. A powder with a wide particle size distribution between 200 ~m and 2000 E.cm is obtained. The fraction above 1 atat was screened off and returned to the process.
Example 7:
A pharmaceutical agent (dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, trivial name: nifedipine) was treated by the PGSS pro-cess . Carbon dioxide was dissolved in the product at a temperature of 145°C and under a pressure of 200 bar. A
powder with an average particle size of 10 ~,m was obtained by spraying through a nozzle. The mass ratio of gas to solid in the present case is 0.1:1.
Example 8:
Carbon dioxide is dissolved under a pressure of 80 bar in glycerol 1-stearic ester at a temperature of 85°C. The mass ratio between carbon dioxide and mono-stearate is 0.18:1. Immediately before spraying through a nozzle, nitrogen is metered into the gas-containing liquid. The ratio of the mass flows of nitrogen to gas-containing liquid is 0.5:1. After decompression in the nozzle (height of fall about 1.8 m), a fine-particle white powder with an average particle size of 8.2 N,m is obtained. This example essentially corresponds to Example 4. However, finer particles are obtained by metering in the foreign gas stream.
References:
/1/ Tavana A., Randolph A.D., Aiche Journal 1989, 35(10) /2/ Bush P.J., Pradhan D., Ehrlich P., Macromolecules 1991, 24(6) 1439 /3/ Chang C.J., Randolph A.D., Aiche Journal 1990, 36(6) ~~.~2 ~~ f /4/ Tom W.J., Debenedetti P.G., Biotechnol. Prog. 1991, 7, 403 /5/ Matson D.W., Petersen R.G., Smith R.; Advances in Ceramics 1987, 21, 1090
In addition to the thermal energy requirement, considerable amounts of energy are needed for mechanical recompression of the large amounts of gas.
Similar factors also apply to the RESS process.
In this case too, very high pressures of, in some cases, above 600 bar /5/ and large excesses of gas are necessary to dissolve solids in the supercritical fluid. Processes requiring several hundred kilograms of gas to obtain 1 kg of powder are described.
It is likewise known from gas extraction that supercritical media have a poor dissolving capacity for very many substances. Hence very high pressures and large amounts of solvent are necessary both in gas extraction and in the processes described above for producing particles.
Description of the invention The invention is based on the object of providing a process which avoids the abovementioned disadvantages of the classical processes and of the high-pressure processes.
This object is achieved according to the invention by a process which comprises the steps stated in claim 1. Preferred embodiments and further developments of the process according to the invention are indicated in the dependent claims.
The process according to the invention is based on the surprising finding that it is unnecessary to start from supercritical solutions to produce particles. On the contrary, it is entirely sufficient to dissolve gases or, in general, compressible fluids in the substance to be treated. The solution produced in this way, which is preferably saturated with compressible fluid, is rapidly decompressed in a suitable decompression apparatus. When the compressible fluid used is a gas, this escapes on decompression and brings about a cooling which is so great that the temperature falls below the solidification point of the substance to be treated. The substance precipitates in fine-particle form and is removed from the stream of gas by suitable processes (for example sedimentation, cylone, filtration, electrofiltration) and, if required, fractionated. Since the procedure is as just described, the process according to the invention is also referred to hereinafter as the PGSS process (Particles from Gas Saturated Solutions).
The substance to be treated can be either a solid or a liquid under ambient conditions. If the substance to be treated or the mixture of substances to be treated is in the form of a solid, a liquid solution under pressure is produced by dissolving the compressible fluid. The mass ratio between the compressible fluid and the substance to be treated is in this case between 0.1:1 and 4:1 and is thus 2 to 3 orders of magnitude less than in the other high-pressure process techniques for producing solids.
The solubility of gases in liquids is considerably greater than that of liquids/solids in gases. Thus, the solubility of stearic acid in ethane at a temperature of 80°C and under a pressure of 37 bar is 0.002% by weight. However, the solubility of ethane in stearic acid under the same conditions of pressure and temperature is as much as 5.62% by weight. On -decompression of the gas-containing liquid solution of, for 'example, ethane in stearic acid in a suitable apparatus, for example a coa~ercially obtainable high-pressure nozzle, the compressed fluid, in this case ethane, is returned to the gaseous state. It has now been found, surprisingly and unpredictably for the skilled worker, that .the cooling is so great, despite the unusually low gas content, that the temperature falls below the solidification point of the substance to be treated downstream of the decompression apparatus. The substance to be treated therefore precipitates as a fine-particle solid. For the solidification point to be reached it is necessary to comply with certain outline ~~~2 ~~6 conditions concerning the temperatures at which the compressible fluid is dissolved. The guideline is that the temperature before decompression should, in the case of substances or mixtures of substances which have a clearly defined melting point, be in the region of ~50 R, preferably ~20 R, above or below the melting point under atmospheric pressure. The process according to the invention results in solutions of a substance or of a mixture of substances even at temperatures below the melting point of this substance or mixture of substances under standard conditions, that is say under atmospheric pressure. It is thus evident that the melting point of a substance or of a mixture of substances is reduced by dissolving a compressible fluid under pressure. Thus, for example, it has been found that the melting point of glycerol 1-stearic ester, which is at 75°C under atmospheric pressure, declines to 58°C in a carbon dioxide atmosphere of 150 bar. Under a propane atmosphere, a melting point of 58°C is reached under a pressure of only 20 bar.
This fact is of particular importance in the treatment of substances which decompose even before reaching the melting point. It is possible according to the invention, by selecting a suitable compressible fluid, to achieve liquid solutions at temperatures which are distinctly below the decomposition point.
In another embodiment of the process according to the 'invention. the melting point of a substance is reduced by adding an incompressible auxiliary. The incompressible auxiliary is chosen in this case so that it forms a low-melting eutectic with the substance to be sprayed. Then a compressible fluid is dissolved, in the manner described above, in the eutectic mixture formed in this way and the resulting liquid solution is rapidly decompressed. The eutectic mixture solidifies due to the cooling after decompression.
Suitable compressible fluids are a whole series of substances. In a preferred embodiment,. carbon dioxide, short-chain alkanes, dinitrogen monoxide, nitrogen alone ~182'~86 or in mixtures are employed. However, in principle, it is possible to use the vapor phase of any of the substances mentioned in Table 1, and mixtures of these substances, as compressible fluid.
Table 1 Compound Boiling Critical Critical Critical point temperaturepressure density [CJ (CJ Ibar1 fkg/m'1 CO= -78.5 31.. 72.9 0.448 NH3 -33.35 132.4 112.5 0.235 HZO 100.00 374.15 218.3 0.315 l~ N,0 -88.56 36.5 71.7 0.45 CH, -164.00 -82.1 45.8 0.2 Ethane -88.63 32.28 48.1 0.203 Ethylene -103.7 9.21 49.7 0.218 Propane -42.1 96.67 41.9 0.217 1 Propylene -47.4 91.9 45.4 S
n-Butane -0.5 152.0 37.5 i-Butana -11.7 134.7 35.9 n-Peatana 36.1 196.6 33.3 0.232 Benzene 80.1 288.9 48.3 0.302 Methanol 64.7 240.5 78.9 0.272 Ethahol 78.5 243.0 63.0 0.276 Iaopropanol 82.5 235.3 47.0 0.273 Isobutaaol 108.0 275.0 42.4 0.272 Chlorotrifluoromethane-31.2 28.0 38.7 0.579 2 Monofluoromethane 78.9 44.6 58.0 0.3 Toluene 110.6 320.0 40.6 0.292 Pyridine 115.5 347.0 55.6 0.312 Cyclohexane 80.74 280.0 40.2 0.273 Cyclohexanol 155.65 391.0 25.8 0.254 3 o-xylene 149.4 357.0 35.0 0.284 ~ CA 02182786 2003-04-22 The PGSS process provided according to the invention is a particularly interesting and universal alternative to conventional processes for producing particles. The main advantages compared with conventional processes are:
~ considerably lower pressures than in crystallization from supercritical solutions or in the RESS process ~ excellent flexibility and considerably smaller gas requirement because of the good solubility of the compressible fluids in liquids; 0.1 - 1 kg of gas per kilogram of solid produced is typical, and this value is unusually low by comparison with classical processes for producing solids, for example spray drying, spray crystallization and low-temperature grinding, since gases are required in the form of drying media or as cooling medium in the processes just mentioned. Typical figures for gas usage are therefore between 2 and 20 kg of gas/kg of solid in those cases.
~ possibility of circulating the gas after the solids have separated out ~ no waste streams or residual solvents to be disposed of ~ the solid particles produced are free of solvent ~ the PGSS process can be applied successfully to products which cannot be powdered by other processes (for example waxes and resins or else polymeric compounds with unusual rheological properties) ~ the process is suitable for thermally sensitive substances because low temperatures can be used ~ the process is also suitable for powdering mixtures of substances; the temperature at which the gas dissolves can be influenced in very wide limits by suitable selection of incompressible auxiliaries ~ dust explosions are avoided when inert gases are used as compressible media.
In accordance with another aspect of the present invention, there is provided a process for the production 8a of particles or powders, in particular of solid particles, having the steps:
provision of a pressure vessel which contains a substance or mixture of substances to be treated, dissolution of a compressible fluid under pressure in the substance or mixture of substances provided, until a solution forms, decompression of the resulting solution by means of a decompression apparatus in such a way that the temperature fails below the solidification point of the substance or mixture of substances downstream of the decompression apparatus, and formation of particles takes place, and removal of the particles which have formed from the stream of decompressed compressible fluid.
Preferred examples of the process according to the invention are explained in detail hereinafter, also referring to the appended drawings, which show:
_ g _ Fig. 1 a diagrammatic representation of an apparatus suitable for carrying out the process according to the invention, and.
Fig. 2 a particle size distribution obtained in one test (see Example 4).
An apparatus suitable for carrying out the process according to the invention is explained in detail by means of Fig. 1. A substance to be treated or a mixture of substances to be treated is melted in a feed vessel A. An autoclave C (V=5 liter, pm"~=400 bar, T~=250°C) is evacuated before starting the test.
Subsequently, the molten substance or mixture of substances is sucked in. The compressible fluid is conveyed into the autoclave up to the required pressure using a high-pressure pump H which is operated by compressed air in this case. The pressure is measured by an analog manometer (0-600 bar).
A high-pressure circulating pump E is used to draw off the liquid phase at the base of the autoclave and convey it to the top of the autoclave C. The liquid phase circulation intensifies material exchange between the liquid and gaseous phase; the rate of dissolution of the gas in the liquid is increased. During the dissolution of the gas. the pressure and temperature are manually corrected where appropriate via control loops.
The autoclave is provided with sampling devices with whose aid it is possible to measure the gas content in the liquid phase. When the required gas content is reached, the spray process is initiated. To do this, the gas-containing liquid is passed via a thermostated line to the top of a spray tower F which has previously been evacuated by means of a vacuum pump and/or flushed with inert gas (for example COz, Nz), in order to preclude the danger of dust explosions with atmospheric oxygen. The gas-containing liquid is decompressed through a suitable decompression apparatus, for example a high-pressure - nozzle. It is also possible alternatively to employ other decompression elements (manual valve,. control valve, capillaries, orifices etc.). In another embodiment it is X18? r~~
-possible for an additional gas stream to be metered in directly upstream of the nozzle or in the nozzle. Smaller particle sizes can be obtained in this way.
The mass flow of gas-containing liquid fed to the 5 spray tower can be measured by a mass flow apparatus according to the Coriolis principle. In order to avoid a fall in pressure in the autoclave during the spray process, fresh, preheated gas is metered into the top of the autoclave by the high-pressure pump B.
10 On decompression of the solution containing the compressed fluid, the compressible fluid is converted into the gaseous state. This results in cooling of the mixture of compressible fluid and substance or mixture of substances to be powdered, and in precipitation of solid.
The temperature and the temperature distribution in the spray tower can be measured with displaceable thermoelements. The spray tower has dimensions such that preferentially particles with an equivalent diameter of 10 N.m are deposited by sedimentation. The particles are collected in a discharge vessel or can be continuously discharged using a suitable apparatus (airlock, screw, fluidized bed with overflow inter alia). The spray tower can be provided with viewing windows to inspect the spray process.
The gas stream from which the larger particles have been removed leaves the spray tower at the upper end and is fed to a cyclone. The cyclone has dimensions such that preferentially particles with a size above 1 ~.m are deposited. The particles are collected in a discharge vessel fixed on the lower end of the cyclone.
To remove particles below 1 Vim, the gas stream leaving the cyclone is passed through an electric field in an electrostatic precipitator. The supply voltage is 20 kV. The particles are deposited on a central wire and shaken off at regular intervals. It is also possible. as an alternative to the electrostatic precipitator, to employ other fine filters (for example fabric filters and the like).
The residual gas is passed out of the system ~~8~ ~~~
through a volume flow gauge and can be recompressed and returned to the autoclave. The gas can also, where appropriate, be continuously extracted from the system by means of a blower.
The system and mode of operation described comprise one possible embodiment of the process. Refer-ence has been made to some other embodiments and modifi-cations. Other industrially relevant alternatives com-prise in particular the generation of the required solution from compressible fluid and substance or mixture of substances to be treated. It is possible in this case to employ, in place of the autoclave C, for example a static mixer in which the material exchange between liquid and compressible fluid is particularly efficient.
The process can be operated continuously when a static a~,xer is used.
Examples Example 1:
Glyceride mixtures from palm kernel oil which are starting materials for producing emulsifiers and deter gents are sprayed using propane. The melting point of the product, which consists of 60~ monoglycerides, 37~
diglycerides and 2~ triglycerides, and 1% free fatty acids, is 44°C. The product is saturated with propane in an autoclave at a -emperature of 45°C and under a pres-sure'of 260 bar and sprayed through a nozzle. The height of free fall after emerging from the nozzle is 0.25 m. A
fine-particle powder with an average particle size of 10.5 N.m is obtained. The temperature of the powder i~ediately after spraying is 0°C. The apparent density of the powder is 80 g/1.
Example 2:
The mixture from Example 1 forms a liquid solu tion with propane under a pressure of 230 bar and at a temperature of 37°C (which is 7°C below the melting point under atmospheric conditions). The propane-containing ~1~~ ~8 (about 35~ by weight) glycerides are sprayed through a nozzle. The height of fall after emerging from the nozzle is 1.0 m. The average particle size is 9.5 ~.m. The temperature after decompression is -3°C. The apparent density of the resulting powder is 55 g/1.
Example 3:
Propane is dissolved in the glyceride mixture from Example 1 at a temperature of 47°C and under a pressure of 20 bar. The propane content is 22~ by weight.
The liquid solution formed in this way is sprayed through a nozzle. The height of fall after emerging from the nozzle is 1.0 m. The average particle size is 25 Vim. The temperature after decompression is 30°C.
Example 4:
Monoglycerides of stearic acid are employed on a large scale as physiologically acceptable, highly effec-tive emulsifier in food technology. A glycerol 1-stearic ester with a melting point of 75°C and a purity of 99~ by weight is sprayed. Carbon dioxide is dissolved under a pressure of 80 bar in the monostearate at a temperature of 85°C. The mass ratio between carbon dioxide and monostearate is 0.18:1. After spraying through a nozzle (height of fall about 1.8 m), a fine-particle white powder with an average particle size of 12.8 ~m and an apparent density of 39 g/1 is obtained. A powder with an average particle size of 7.8 Ecm is drawn off from the cyclone. A few mg of particles with a particle size < 1 ~Cm are deposited in the electrostatic precipitator.
The particle size and particle size distribution of the powder drawn off from the spray tower are shown in Fig.
2, and the numerical values are shown in Tab. 2.
~~~~~8 Table 2 Diameter 0.7 0.9 1.0 1.4 1.7 2.0 2.6 3.2 4.0 S.0 Total % contents5.2 5.9 6.2 7.5 8.7 10.213.015.417.8 20.1 by mass Diameter 6.0 8.0 10.012.0 15.018.023.030.036.0 95.0 ~m Total % coatents22.2 26.028.130.3 36.548.273.497.1100 100 by mass 1 Diameter 56.0 70.090.010 35 65 210 60 320 400 ~m Total % conteats100 100 00 00 00 00 100 00 100 100 by mass Example 5:
Citric acid has a melting point of 156°C under atmospheric pressure. Citric acid is mixed in the mass ratio 1:3 with polyethylene glycol having an average molecular weight of 1500 g/mol and a melting range of 44-48°C. The mixture produced in this way melts in a temperature range between +2 and +5°C, that is to say the two substances form a eutectic with a melting point below the melting points of the two pure substances. Carbon dioxide is dissolved under a pressure of 200 bar in the mixture of citric acid and polyethylene glycol in a pressure vessel at a temperature of 20°C. The gas-con- -taining solution formed in this way is decompressed in a nozzle. A coprecipitate of citric acid and polyethylene glycol in powder form with a temperature of -5°C results.
The average particle size is 300 Vim. It is accordingly possible, by adding a suitable auxiliary, to reduce the temperature at which the required product (in this case citric acid) is to be saturated with gas considerably below the melting point of the product under atmospheric conditions.
Example 6:
Carbon dioxide is dissolved under a pressure of 200 bar in a polyether with an average molecular weight ~1~2'~~
of 3500 g/mol and a melting point of 42°C at a tempera-ture of 45°C. The gas-containing solution is decompressed through a manually operated metering valve into a col-lecting vessel. The height of the fall to the bottom of the collecting vessel is about 0.4 m. A powder with a wide particle size distribution between 200 ~m and 2000 E.cm is obtained. The fraction above 1 atat was screened off and returned to the process.
Example 7:
A pharmaceutical agent (dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate, trivial name: nifedipine) was treated by the PGSS pro-cess . Carbon dioxide was dissolved in the product at a temperature of 145°C and under a pressure of 200 bar. A
powder with an average particle size of 10 ~,m was obtained by spraying through a nozzle. The mass ratio of gas to solid in the present case is 0.1:1.
Example 8:
Carbon dioxide is dissolved under a pressure of 80 bar in glycerol 1-stearic ester at a temperature of 85°C. The mass ratio between carbon dioxide and mono-stearate is 0.18:1. Immediately before spraying through a nozzle, nitrogen is metered into the gas-containing liquid. The ratio of the mass flows of nitrogen to gas-containing liquid is 0.5:1. After decompression in the nozzle (height of fall about 1.8 m), a fine-particle white powder with an average particle size of 8.2 N,m is obtained. This example essentially corresponds to Example 4. However, finer particles are obtained by metering in the foreign gas stream.
References:
/1/ Tavana A., Randolph A.D., Aiche Journal 1989, 35(10) /2/ Bush P.J., Pradhan D., Ehrlich P., Macromolecules 1991, 24(6) 1439 /3/ Chang C.J., Randolph A.D., Aiche Journal 1990, 36(6) ~~.~2 ~~ f /4/ Tom W.J., Debenedetti P.G., Biotechnol. Prog. 1991, 7, 403 /5/ Matson D.W., Petersen R.G., Smith R.; Advances in Ceramics 1987, 21, 1090
Claims (15)
1. A process for the production of particles or powders, in particular of solid particles, having the steps:
provision of a pressure vessel which contains a substance or mixture of substances to be treated, dissolution of a compressible fluid under pressure in the substance or mixture of substances provided, until a solution forms, decompression of the resulting solution by means of a decompression apparatus in such a way that the temperature fails below the solidification point of the substance or mixture of substances downstream of the decompression apparatus, and formation of particles takes place, and removal of the particles which have formed from the stream of decompressed compressible fluid.
provision of a pressure vessel which contains a substance or mixture of substances to be treated, dissolution of a compressible fluid under pressure in the substance or mixture of substances provided, until a solution forms, decompression of the resulting solution by means of a decompression apparatus in such a way that the temperature fails below the solidification point of the substance or mixture of substances downstream of the decompression apparatus, and formation of particles takes place, and removal of the particles which have formed from the stream of decompressed compressible fluid.
2. The process as claimed in claim 1, wherein the pressure during the dissolution is in the range from 5 to 500 bar.
3. The process as claimed in claim 1, wherein the pressure during the dissolution is in the range from 10 to 200 bar.
4. The process as claimed in any one of claims 1 to 3, wherein the solution obtained after the dissolution of the compressible fluid is kept at a temperature which is in the region of up to 50 K above or below the melting point under atmospheric pressure of the substance or mixture of substances to be treated.
5. The process as claimed in any one of claims 1 to 3, wherein the solution obtained after the dissolution of the compressible fluid is kept at a temperature which is in the region of up to 20 K above or below the melting point under atmospheric pressure of the substance or mixture of substances to be treated.
6. The process as claimed in any one of claims 1 to 3, wherein the solution obtained after the dissolution of the compressible fluid is kept at a temperature which is in the region of up to 10 K above or below the melting point under atmospheric pressure of the substance or mixture of substances to be treated.
7. The process as claimed in any one of claims 1 to 6, wherein in the case of substances or mixtures of substances which decompose on heating under atmospheric pressure before they melt, the solution obtained after dissolution of the compressible fluid Is kept at a temperature which is below the decomposition temperature under atmospheric pressure of the substance or mixture of substances to be treated.
8. The process as claimed in any one of claims 1 to 7, wherein the melting point of the substance or mixture of substances to be treated is reduced by means of an incompressible auxiliary which is added before, during or after dissolution of the compressible fluid.
9. The process as claimed in claim 8, wherein the incompressible auxiliary forms a low-melting eutectic with the substance or mixture of substances to be treated.
10. The process as claimed in any one of claims 1 to 9, wherein the compressible fluid is selected from the group of hydrocarbons with 1 to 6 C
atoms.
atoms.
11. The process as claimed in any one of claims 1 to 9, wherein the compressible fluid is selected from the group of methane, ethane, propane, butane, pentane, n-hexane, i-hexane, carbon dioxide, freons, nitrogen, inert gases, gaseous oxides, for example N2O, SO2, ammonia, alcohols with 1 to 4 C atoms, in particular methanol, ethanol, isopropanol, n-propanol, butanol, halogenated hydrocarbons or mixtures of the abovementioned substances.
12. The process as claimed in any one of claims 1 to 11, wherein the particles which are formed are removed in fractions.
13. The process as claimed in claim 12, wherein the particle stream is passed, for the fractional removal, first through a spray tower, then through a cyclone and finally through a fine filter.
14. The process as claimed in claim 13, wherein the fine filter is an electrostatic precipitator.
15. The process as claimed in any one of claims 1 to 14, wherein the resulting solution is decompressed through a nozzle or a valve or a diffuser or a capillary.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| SI9400079A SI9400079B (en) | 1994-02-15 | 1994-02-15 | Method and device for extraction and fractionation of small particles from solutions saturated with gas |
| SI94/00079 | 1994-02-15 | ||
| PCT/EP1995/000538 WO1995021688A1 (en) | 1994-02-15 | 1995-02-14 | Process for preparing particles or powders |
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| CA2182786A1 CA2182786A1 (en) | 1995-08-17 |
| CA2182786C true CA2182786C (en) | 2003-12-30 |
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| EP (1) | EP0744992B1 (en) |
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Families Citing this family (77)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6576264B1 (en) | 1995-10-17 | 2003-06-10 | Skyepharma Canada Inc. | Insoluble drug delivery |
| CN1233169A (en) * | 1996-10-14 | 1999-10-27 | 弗·哈夫曼-拉罗切有限公司 | Process for the manufacture of a pulverous preparation |
| JP3492317B2 (en) * | 1997-10-06 | 2004-02-03 | アーダルベルト−ラプス−シュティフツング | Process for producing powdery products from liquid substances or mixed substances |
| DE19749989A1 (en) | 1997-11-12 | 1999-05-27 | Herberts Gmbh | Process for the preparation of powder coating compositions |
| GB9804379D0 (en) * | 1998-03-02 | 1998-04-22 | Bradford Particle Design Ltd | Method of particle formation |
| WO1999052504A1 (en) * | 1998-04-09 | 1999-10-21 | F. Hoffmann-La Roche Ag | Process for the manufacture of (sub)micron sized particles by dissolving in compressed gas and surfactants |
| JP3812135B2 (en) * | 1998-04-15 | 2006-08-23 | 石川島播磨重工業株式会社 | Method for supercritical and hydrothermal reaction treatment of organic matter and treatment plant |
| CA2335472C (en) | 1998-06-19 | 2008-10-28 | Rtp Pharma Inc. | Processes to generate submicron particles of water-insoluble compounds |
| DE19833543A1 (en) | 1998-07-25 | 2000-01-27 | Messer Griesheim Gmbh | Extrusion of plastic to make powders, particulates, powder coatings, colors, dyes and inks, injects e.g. carbon dioxide into extruder to reduce duroplastic viscosity and promote foaming and comminution at exit |
| DE19860497A1 (en) | 1998-12-28 | 2000-07-06 | Basf Ag | Method and device for producing stably fine powder |
| US6630121B1 (en) | 1999-06-09 | 2003-10-07 | The Regents Of The University Of Colorado | Supercritical fluid-assisted nebulization and bubble drying |
| GB9915975D0 (en) | 1999-07-07 | 1999-09-08 | Bradford Particle Design Ltd | Method for the formation of particles |
| PT1263413E (en) * | 2000-03-09 | 2006-08-31 | Univ Ohio State Res Found | METHOD OF PREPARING SOLID SCATTERS |
| WO2001087277A2 (en) * | 2000-05-15 | 2001-11-22 | Vectura Limited | Method of manufacturing particles |
| FR2811913B1 (en) * | 2000-07-19 | 2003-09-19 | Separex Sa | ENCAPSULATION PROCESS IN THE FORM OF MICRO-CAPSULES OF FINE SOLID PARTICLES |
| DE10040551A1 (en) | 2000-08-15 | 2002-02-28 | Bayer Ag | Process for the production of polyurethane particles |
| ES2170008B1 (en) | 2000-08-25 | 2003-05-01 | Soc Es Carburos Metalicos Sa | PROCEDURE FOR THE PRECIPITATION OF SOLID PARTICLES FINALLY DIVIDED. |
| DE10042553A1 (en) * | 2000-08-30 | 2002-03-28 | Messer Griesheim Gmbh | Method and device for monitoring the material composition of fluid, separable media |
| DE10054114A1 (en) | 2000-10-31 | 2002-05-16 | Dupont Performance Coatings | Process for the preparation of powder coating compositions |
| GB0027357D0 (en) | 2000-11-09 | 2000-12-27 | Bradford Particle Design Plc | Particle formation methods and their products |
| EP1354581A4 (en) * | 2000-12-26 | 2007-07-04 | Takeda Pharmaceutical | Porous substance and process for producing the same |
| DE10105801B4 (en) | 2001-02-07 | 2004-07-08 | Henkel Kgaa | Detergents and cleaning agents comprising fine microparticles with detergent components |
| GB0108995D0 (en) | 2001-04-10 | 2001-05-30 | Nokia Corp | Provisioning services to groups of subscribers |
| DE60118983T3 (en) * | 2001-07-02 | 2016-07-07 | Micro & Nano Materials Sagl | Process for the preparation of nano and micro particles |
| GB0117696D0 (en) | 2001-07-20 | 2001-09-12 | Bradford Particle Design Plc | Particle information |
| GB0208742D0 (en) | 2002-04-17 | 2002-05-29 | Bradford Particle Design Ltd | Particulate materials |
| GB0205868D0 (en) * | 2002-03-13 | 2002-04-24 | Univ Nottingham | Polymer composite with internally distributed deposition matter |
| WO2003088951A1 (en) * | 2002-04-15 | 2003-10-30 | Eiffel Technologies Limited | Formulation of fine particles using liquefied or dense gases |
| PL372905A1 (en) * | 2002-04-29 | 2005-08-08 | Bristol-Myers Squibb Company | Crystallization system utilizing atomization |
| US9339459B2 (en) | 2003-04-24 | 2016-05-17 | Nektar Therapeutics | Particulate materials |
| CN1652852A (en) * | 2002-05-10 | 2005-08-10 | 布里斯托尔-迈尔斯斯奎布公司 | Crystallization system using homogenization |
| DE10248619A1 (en) * | 2002-10-18 | 2004-04-29 | Bayer Ag | Process for the preparation of powdered active substance formulations with compressible fluids |
| FR2847486B1 (en) * | 2002-11-21 | 2005-02-04 | Centre Nat Rech Scient | PROCESS FOR PRODUCING PARTICLES |
| FR2847487B1 (en) * | 2002-11-21 | 2005-02-18 | Centre Nat Rech Scient | PROCESS FOR PRODUCING PARTICLES |
| KR20060015587A (en) | 2003-05-08 | 2006-02-17 | 넥타 쎄라퓨틱스 유케이 리미티드 | Particulate materials |
| ES2414091T3 (en) | 2003-07-17 | 2013-07-18 | Unilever N.V. | Stabilization process of an edible dispersion comprising oil |
| WO2005022603A2 (en) * | 2003-09-02 | 2005-03-10 | Integral Technologies, Inc. | Low cost conductive containers manufactured from conductive loaded resin-based materials |
| WO2005053851A1 (en) * | 2003-11-26 | 2005-06-16 | E.I. Dupont De Nemours And Company | High pressure media milling system and process of milling particles |
| AU2004298723B2 (en) * | 2003-12-19 | 2008-07-10 | Scf Technologies A/S | Systems for preparing fine particles and other substances |
| US20050170063A1 (en) * | 2004-01-29 | 2005-08-04 | Lalit Chordia | Production of powder and viscous material |
| FR2874836B1 (en) * | 2004-09-09 | 2007-04-27 | Pierre Fabre Medicament Sa | PROCESS FOR COATING POWDERS |
| CA2587636A1 (en) * | 2004-11-17 | 2006-05-26 | Massachusetts Institute Of Technology | Frozen food production |
| CN1302881C (en) * | 2004-12-10 | 2007-03-07 | 华东理工大学 | Method and apparatus for preparing superfine powder by super high pressure supercritical fluid micro jetting technology |
| PL1885192T3 (en) | 2005-02-17 | 2015-08-31 | Unilever Bcs Europe Bv | Fat granules |
| EP1948717B1 (en) * | 2005-11-17 | 2014-05-21 | Basf Se | Use of a dry powder of a polymeric additive |
| EP2086600B1 (en) * | 2006-11-03 | 2016-10-26 | Boston Scientific Limited | Stents with drug eluting coatings |
| CN101622302B (en) * | 2007-01-26 | 2013-01-23 | Isp投资公司 | Formulation process method to produce spray dried products |
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| ATE522146T1 (en) | 2009-10-23 | 2011-09-15 | Uelzena Eg | METHOD FOR PRODUCING STORAGE-STABLE VACCINE CRYSTALS FROM COCOA BUTTER OR CHOCOLATE MASSES |
| US9924730B2 (en) | 2010-06-22 | 2018-03-27 | Unilever Bcs Us, Inc. | Edible fat powders |
| WO2012024340A2 (en) * | 2010-08-16 | 2012-02-23 | The Johns Hopkins University | Method for extraction and purification of oils from microalgal biomass using high-pressure co2 as a solute |
| HUE026515T2 (en) | 2010-12-17 | 2016-06-28 | Unilever Bcs Europe Bv | Edible water in oil emulsion |
| US20130266715A1 (en) | 2010-12-17 | 2013-10-10 | René Joachim Buter | Process of compacting a microporous fat powder and compacted fat powder so obtained |
| US9808030B2 (en) | 2011-02-11 | 2017-11-07 | Grain Processing Corporation | Salt composition |
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| DE102011085688A1 (en) | 2011-11-03 | 2013-05-08 | Beiersdorf Ag | Cosmetic preparations with powdered hydrophobic substances |
| DE102011085685A1 (en) | 2011-11-03 | 2013-05-08 | Beiersdorf Ag | Cosmetic preparation with powdered substances to improve the perfume adhesion |
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| PL2897464T3 (en) | 2012-09-21 | 2016-06-30 | Unilever Bcs Europe Bv | Edible water-in-oil emulsion and a process for preparing such emulsion |
| US10750759B2 (en) | 2012-09-21 | 2020-08-25 | Upfield Europe B.V. | Edible water-in-oil emulsions and a process for preparing such emulsions |
| US9394314B2 (en) | 2012-12-21 | 2016-07-19 | Map Pharmaceuticals, Inc. | 8′-hydroxy-dihydroergotamine compounds and compositions |
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| CA2934413A1 (en) | 2013-12-20 | 2015-06-25 | Philip Morris Products, S.A. | Wax encapsulated flavour delivery system for tobacco |
| WO2015180922A1 (en) | 2014-05-26 | 2015-12-03 | Sabic Global Technologies B.V. | Method for producing clean thermoplastic particles |
| US11136438B2 (en) | 2015-07-13 | 2021-10-05 | Sabic Global Technologies B.V. | Process for the preparation of polyolefin particles |
| WO2018001486A1 (en) * | 2016-06-30 | 2018-01-04 | Sabic Global Technologies B.V. | Process for the preparation of polyolefin particles |
| JP5972435B1 (en) * | 2015-07-29 | 2016-08-17 | 長瀬産業株式会社 | Coating liquid composition, method for producing coating liquid composition, and composition for preparing coating liquid composition |
| JP5923677B1 (en) * | 2016-03-09 | 2016-05-24 | 長瀬産業株式会社 | Coating liquid composition, coating film forming method, coating liquid composition manufacturing method, coating liquid composition manufacturing apparatus, and carbon dioxide-containing coating liquid composition preparation composition |
| US11130850B2 (en) | 2017-01-02 | 2021-09-28 | Sabic Global Technologies B.V. | Process for recycling polyolefin |
| EP4190437A1 (en) | 2021-12-03 | 2023-06-07 | SiTec PharmaBio SL | Process and apparatus for the manufacture of solid microparticles |
Family Cites Families (14)
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|---|---|---|---|---|
| US19456A (en) * | 1858-02-23 | Improvement in seed-planters | ||
| USRE19456E (en) | 1935-02-12 | Process of producing powdered soap | ||
| US1308403A (en) * | 1919-07-01 | Process oe hrobtj cim g- dbhybbateb mineral salts | ||
| US997502A (en) * | 1910-05-31 | 1911-07-11 | Paul Kestner | Process of evaporating liquids. |
| US1673685A (en) * | 1927-06-15 | 1928-06-12 | Naugatuck Chem Co | Method of and apparatus for treating solutions and products |
| US3450494A (en) * | 1967-07-18 | 1969-06-17 | Conrad J Gaiser | Amorphous sodium silicate having inherent binding properties and method of producing same |
| JPS5653104A (en) * | 1979-10-09 | 1981-05-12 | Mitsui Petrochem Ind Ltd | Separation of polymer from polymer solution |
| DE3009602A1 (en) * | 1980-03-13 | 1981-10-01 | Basf Ag, 6700 Ludwigshafen | METHOD FOR SHAPING ORGANIC PIGMENTS |
| DE3744329A1 (en) * | 1987-12-28 | 1989-07-06 | Schwarz Pharma Gmbh | METHOD FOR THE PRODUCTION OF AT LEAST ONE ACTIVE AGENT AND A TRAITER COMPRISING PREPARATION |
| JPH01176437A (en) * | 1987-12-29 | 1989-07-12 | Ono Pharmaceut Co Ltd | Method for rendering organic substance into fine particles |
| US5066522A (en) * | 1988-07-14 | 1991-11-19 | Union Carbide Chemicals And Plastics Technology Corporation | Supercritical fluids as diluents in liquid spray applications of adhesives |
| JP2774349B2 (en) * | 1990-03-17 | 1998-07-09 | 株式会社神戸製鋼所 | Manufacturing method of fine particles |
| JPH04156902A (en) * | 1990-10-17 | 1992-05-29 | Masayuki Yokota | Method and device for drying by explosive vaporization |
| US6063910A (en) * | 1991-11-14 | 2000-05-16 | The Trustees Of Princeton University | Preparation of protein microparticles by supercritical fluid precipitation |
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1994
- 1994-02-15 SI SI9400079A patent/SI9400079B/en unknown
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1995
- 1995-02-14 ES ES95909720T patent/ES2109095T3/en not_active Expired - Lifetime
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- 1995-02-14 DK DK95909720.5T patent/DK0744992T3/en active
- 1995-02-14 DE DE59500808T patent/DE59500808D1/en not_active Expired - Lifetime
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- 1995-02-14 AT AT95909720T patent/ATE159184T1/en active
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1997
- 1997-11-07 US US08/965,805 patent/US6056791A/en not_active Expired - Lifetime
- 1997-11-26 GR GR970403144T patent/GR3025495T3/en unknown
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| WO1995021688A1 (en) | 1995-08-17 |
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| JP3510262B2 (en) | 2004-03-22 |
| EP0744992B1 (en) | 1997-10-15 |
| DK0744992T3 (en) | 1998-06-02 |
| DE59500808D1 (en) | 1997-11-20 |
| CA2182786A1 (en) | 1995-08-17 |
| ATE159184T1 (en) | 1997-11-15 |
| JPH09508851A (en) | 1997-09-09 |
| ES2109095T3 (en) | 1998-01-01 |
| GR3025495T3 (en) | 1998-02-27 |
| SI9400079B (en) | 2003-02-28 |
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