Method for producing particulate goods

• US 6,584,782 B2
• Filed: 08/08/2002
• Issued: 07/01/2003
• Est. Priority Date: 02/25/2000
• Status: Expired due to Term

• Current Assignee: Glatt GmbH (Martina Nowak)
• Original Assignee: Glatt GmbH (Martina Nowak)
• Inventors: Leuenberger, Hans, Luy, Bernhard, Prasch, Armin Karl Theodor
• Primary Examiner(s): Esquivel, Denise L.
• Assistant Examiner(s): Drake, Malik N.
• Application Number:
  US10/182,715
• Publication Number:
  US 20030000228A1
• Time in Patent Office: 327 Days
• Field of Search: 62/57, 62/62, 62/64, 62/67, 62/69
• US Class Current: 62/64
• CPC Class Codes: B01J 2/16 by suspending the powder material in a gas, e.g. in fluidised beds or as a falling curtain
• CPC Class Codes: F26B 3/08 so as to loosen them, e.g. to form a fluidised bed "fluidised-bed" technique in general B01J8/24; centrifugal fluidised beds F26B7/007
• CPC Class Codes: F26B 5/065 the product to be freeze-dried being sprayed, dispersed or pulverised

Abstract

In the method for producing a particulate material (58) from an at least partially liquid material (35) containing a solvent and/or dispersant, this material (35) is atomized in a process chamber (21) into droplets which are frozen to particles (131) by contact with a freezing fluid. The particles (131) are then dried by freeze-drying in the or in another process chamber (22) having a filter (18) at the top. For the freeze-drying, cooled process gas is passed upward from below through the process chamber (22) and through the filter (18) in such a way that at least a substantial part of the particles (131) rest against the filter (18) at least for a substantial part of the freeze-drying taking place in the process chamber (22). This makes it possible to dry a batch of particles (131) in a short time.

Claims

1. Method for producing a particulate material (58) from an at least partially liquid material (35, 235) containing a solvent and/or dispersant, characterized in that the at least partially liquid material (35, 235) is atomized to give droplets and these are frozen by contact with a freezing liquid to give particles (131), that the particles (131) are then at least partly dried by freeze-drying in a process chamber (22) having a filter (18) at the top, and that, during the freeze-drying, process gas is passed upward from below through the process chamber (22) and through the filter (18) in such a way that at least a substantial part of the particles (131) rest against the filter (18) at least during a substantial part of the freeze-drying taking place in the process chamber (22).

2. Method according to claim 1, characterized in that particles (131) resting against the filter (18) during the freeze-drying are detached from the filter (18) from time to time and then caused to rest against the filter (18) again by means of the process gas and further dried on said filter.

3. Method according to claim 2, characterized in that the filter (18) used for the freeze-drying has at least one filter element (18a) which is freed, at least every hour, at least from the major part of the particles (131) resting against it.

4. Method according to claim 1, characterized in that the filter (18) used for the freeze-drying has at least two filter elements (18a) which are freed, during the freeze-drying, separately and alternately from particles (131) resting against them.

5. Method according to claim 3, characterized in that the or each filter (18) is vibrated and/or treated with ultrasound and/or blown out to detach the particles (131) adhering to it.

6. Method according to claim 1, characterized in that a particle batch is formed by successive atomization of liquid and freezing of the droplets and that at least most of the particles (131) rest against the filter (18) for at least 30%, expediently at least 50% and preferably at least 70% of a freeze-drying period in which the particles (131) are dried after production of the particle batch by freeze-drying.

7. Method according to claim 1, characterized in that the process gas passed into the process chamber (22) containing the particles (131) for freeze-drying said particles has a higher temperature than the freezing fluid, the freezing fluid preferably having a temperature which is at most −

30°

C. and, for example, −

80°

C. to −

40°

C., and the temperature of the process gas passed into the process chamber (22) containing the particles (131) for freeze-drying said particles expediently being at least 10°

C. higher, preferably at least 20°

C. higher and, for example, at least 30°

C. higher than the temperature of the freezing fluid and, for example, at least −

30°

C. and, for example, less than 0°

C.

8. Method according to claim 1, characterized in that, for the formation of the freezing fluid, process gas is cooled and is passed into a freezing region serving for freezing the droplets and/or that a coolant (236) which preferably comprises a liquefied gas, for example liquid nitrogen, or dry, pulverulent carbon dioxide or acetone and carbon dioxide dissolved therein is sprayed into the freezing region, for example at least one jet of the at least partially liquid material (235) being produced and, for example, coolant (236) being atomized around a region of this jet.

9. Method according to claim 1, characterized in that the atomization and freezing of the at least partially liquid material (35, 235) is effected in a first process chamber (21, 221) which is connected by a transfer connection (53) to the second process chamber (22) serving for the freeze-drying, that process gas is passed into the first process chamber (21, 221), during the atomization and freezing of the at least partially liquid material (35, 235), through a gas-permeable base (17) arranged at the bottom of the first process chamber (21, 221), and that the particles (131) formed in the first process chamber (21, 221) by freezing are transferred with gas through the transfer connection (53) into the second process chamber (22), a particle batch being produced, for example, by successive freezing of the particles (131) in the first process chamber (21, 221), the particles (131) already present being fluidized during the production of fresh particles (131), and the particles (131) being transferred after the freezing of the entire particle batch into the second process chamber (22), or, for example, the particles (131) formed by freezing being transferred continuously during the production of a particle batch from the first process chamber (21, 221) into the second process chamber (22), and the transfer connection (53) possibly being in the form of a fluidizing channel having a base which is gas-permeable at least in parts and gas possibly being passed through a gas-permeable base of the transfer connection (53) into the latter during the transfer of the particles (131), so that the particles (131) are, for example, fluidized in the transfer connection (53) and, for example, already subjected to a freeze-drying.

10. Method according to claim 1, characterized in that, after the freeze-drying in the process chamber (22) used for this, the particles (131) are transferred through a transfer connection (54) into another, last process chamber (23), the process gas which has a temperature which is more than 0°

C. and, for example, at least 10°

C. to, for example, at most 30°

C. is passed upward from below through this last process chamber (23), and that the particles are fluidized and dried in the last process chamber (23).

11. Method according to claim 9, characterized in that walls (15, 215), gas-permeable bases (17), filters (18, 218) and other parts which bound the process chambers (21, 22, 23) and a passage (61) of the or each transfer connection (53, 54) are made sterile, before and/or after the production of an amount of the particulate material (58), in a state substantially sealed from the environment, by passing in a gaseous and/or a liquid sterilizing agent, for example steam, hot air or liquid alcohol or hydrogen peroxide.

12. Method according to claim 9, characterized in that particles (131) are frozen and dried batchwise and that at least two different process chambers (21, 22, 23, 221) are sealed from one another at least temporarily and simultaneously contain different batches of particles (131).

13. Method according to claim 1, characterized in that gas conveying means (65) are used which, together with the process chamber (22) serving for the freeze-drying, form a gas circulation (72), that the process gas is circulated in the gas circulation (72) through the process chamber (22) in normal phases of operation and that the circulated process gas, after emerging from the process chamber (22) serving for the freeze-drying, is cooled and dried by means of a cooling and drying unit (79) and is then heated in a heating device (80) having a heat exchanger before being passed into the process chamber (22), for example waste heat which is generated by the cooling and drying unit (79) belonging to this gas circulation (72) or, for example, by a cooling and drying unit (79) which belongs to another gas circulation (71) with another process chamber (21, 221) being passed to the heat exchanger and being used therein for heating a process gas.

14. Method according to claim 1, characterized in that energy for heating the particles (131) is supplied to the particles (131) at least during a part of the freeze-drying by electromagnetic radiation and/or waves, for example infrared light and/or microwaves, and/or via the filter (18).

15. Method according to claim 1, characterized in that the pressure of the process gas in the process chamber (22) used for the freeze-drying is lower than the ambient air pressure during at least a part of the freeze-drying, and is possibly at most 900 hectopascal and, for example, 50 hectopascal to 300 hectopascal.

16. Method according to claim 1, characterized in that the originally at least partially liquid material (35, 235) comprises at least one active substance and/or excipient for a drug and/or microorganisms and/or cells for the treatment of humans and/or animals and/or at least one substance for diagnostic purposes, the material being, for example, heat-sensitive.

17. Method according to claim 1, characterized in that the filter (18) bounding the process chamber (22) used for the freeze-drying at the top has a gas-permeable filter area which is greater than a cross-sectional area of a container interior region, containing the filter (18), at the lower end of the filter (18), this filter area expediently being at least 3 times and preferably at least 5 times greater than said cross-sectional area, the filter (18) preferably having at least one approximately vertical, gas-permeable cartridge or at least one approximately vertical, gas-permeable stocking having a length which is expediently at least one 1 m, preferably at least 1.5 m and, for example, at least 2 m, and the process chamber (22) used for the freeze-drying widening upward preferably at least in one region.

18. Method according to claim 1, characterized in that the process chamber (22) used for the freeze-drying is connected by at least one transfer connection (53, 54) to another process chamber (21, 23, 221) having a filter (18, 218) at the top and intended for freeze-drying of the droplets or fluidization and drying of the particles (131), that the filter (18, 218) of each process chamber (21, 22, 23, 221) has at least one gas-permeable stocking or at least one gas-permeable cartridge and that the or each stocking or the or each cartridge of the filter (18) serving for the freeze-drying is longer than the or each stocking or the or each cartridge of the filter (18, 218) belonging to the or another process chamber (21, 23, 22).