Pressure driven flow crystallizer

Patent metadata

Field	Value
Publication number	US-10155786-B2
Application number	US-201615530181-A
Country	US
Kind code	B2
Filing date	Dec 8, 2016
Priority date	Dec 8, 2015
Publication date	Dec 18, 2018
Grant date	Dec 18, 2018

Abstract

The present invention generally relates to systems and methods for pressure driven flow crystallization. In some embodiments, the system comprises a comprising a cavity and a mixing mechanism. In some embodiments, one or more inlets facilitate the transfer of one or more reagent streams to the cavity. In some such embodiments, the mixing mechanism mixes the first and second reagent streams such that a continuous crystallization and/or generation of a product (e.g., solid particles) in the fluid.

First claim

What is claimed:

1. A method comprising:
providing a reaction vessel including at least one inlet for introduction of a reactant, and at least one outlet for recovery of a product, wherein the outlet is constructed and arranged such that it facilitates removal of the product when a volume of substance in the vessel is at least a threshold volume, but not to facilitate removal of the product when a volume of substance in the vessel is below the threshold volume; and
controlling pressure internally of the vessel so as to remove a given volume of the product from the vessel when the volume of substance in the vessel is at least at the threshold volume, while not removing a volume of the product from the vessel when the volume of substance in the vessel is below the threshold volume.

2. A method as in claim 1 , further comprising:
controlling pressure internally of the vessel to release, from the vessel, pressure above a threshold pressure when the volume of substance in the vessel is below the threshold volume.

3. A system comprising:
a reaction vessel including at least one inlet for introduction of a reactant, and at least one outlet for recovery of a product;
a sensor constructed to determine volume of the product in the vessel; and
a conduit in fluid communication with the vessel, and a valve associated with the conduit switchable from a position releasing pressure from the vessel above a threshold pressure, and to apply pressure internally of the vessel upon a signal indicative of a threshold volume of the product in the vessel.

4. A method for crystallizing a compound, comprising:
providing to a cavity of a reaction vessel, through a first inlet fluidically connected to the cavity, a first fluid;
providing to the cavity of the reaction vessel, through a second inlet fluidically connected to the cavity, a second fluid;
mixing the first fluid and the second fluid to form a product;
measuring the volume of the product in the cavity; and
upon reaching a critical vertical volume of the product, applying a pressure to the cavity such that at least a portion of the product flows through a vertically oriented outlet fluidically connected with the cavity to a receiving vessel,
wherein the cavity has a volume of less than 1 L and/or wherein a flow rate of the fluid through the vertically oriented outlet is greater than a sedimentation rate of the product in the fluid.

5. A method as in claim 4 , wherein the receiving vessel is a second reaction vessel.

6. A method for crystallizing a compound, comprising:
providing to a cavity of a reaction vessel, through a first inlet fluidically connected to the cavity, a first fluid;
providing to the cavity of the mixing vessel, through a second inlet fluidically connected to the cavity, a second fluid;
mixing the first fluid and the second fluid to form a product; and
periodically applying a pressure to the cavity such that at least a portion of the product flows through a vertically oriented outlet fluidically connected with the cavity to a receiving vessel, wherein the cavity has a volume of less than 1 L and/or wherein a flow rate of the fluid through the vertically oriented outlet is greater than a sedimentation rate of the product in the fluid.

7. A system, comprising:
a vessel comprising a mixing mechanism and a cavity;
a first inlet fluidically connected to the cavity;
a second inlet fluidically connected to the cavity;
a vertically oriented outlet fluidicially connected to the cavity; and
a pump, configured to apply a pressure to the cavity periodically, wherein
the volume of the cavity is less than 1 L.

8. A system, comprising:
a vessel comprising a mixing mechanism and a cavity;
a first inlet fluidically connected to the cavity;
a second inlet fluidically connected to the cavity;
a vertically oriented outlet fluidicially connected to the cavity;
a fluid height sensor; and
a pump, configured to apply a pressure to the cavity upon a fluid internal to the cavity reaches a critical fluid height, wherein the volume of the cavity is less than 1 L.

9. A method as in claim 4 , wherein the first fluid comprises a crystallizable compound.

10. A method as in claim 4 , wherein the second fluid comprises an antisolvent.

11. A method as in claim 4 , wherein the volume of the cavity is less than 100 mL.

12. A method as in claim 1 , wherein the vessel comprises an antisolvent crystallizer.

13. A method as in claim 1 , wherein the temperature within the vessel is changed during operation.

14. A system as in claim 3 , wherein the reaction vessel is a first reaction vessel and comprising one or more additional reaction vessels fluidically connected in series with the first reaction vessel.

15. A system as in claim 7 , wherein the vessel is a first vessel and comprising one or more additional vessels fluidically connected in series with the first reaction vessel.

16. A method as in claim 1 , wherein the product is a fluid comprising a plurality of suspended solids.

17. A method as in claim 4 , wherein the flow rate of the fluid is less than 10 milliliters per minute.

18. A method as in claim 1 , wherein the product is an active pharmaceutical ingredient.

Assignees

• Massachusetts Inst Technology

Inventors

• Myerson Allan S
• O'Mahony Marcus
• Stelzer Torsten
• Cui Yuqing

Classifications

• C07H17/08 Primary

  Hetero rings containing eight or more ring members, e.g. erythromycins · CPC title

• C07C213/10

  Separation; Purification; Stabilisation; Use of additives · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• B01D9/0036

  Crystallisation on to a bed of product crystals; Seeding · CPC title

• B01D9/0059

  General arrangements of crystallisation plant, e.g. flow sheets · CPC title