Systems and methods for synthesizing chemical products, including active pharmaceutical ingredients

Patent metadata

Field	Value
Publication number	US-11565230-B2
Application number	US-202016988827-A
Country	US
Kind code	B2
Filing date	Aug 10, 2020
Priority date	Aug 15, 2014
Publication date	Jan 31, 2023
Grant date	Jan 31, 2023

Abstract

Systems and methods for synthesizing chemical products, including active pharmaceutical ingredients, are provided. Certain of the systems and methods described herein are capable of manufacturing multiple chemical products without the need to fluidically connect or disconnect unit operations when switching from one making chemical product to making another chemical product.

First claim

What is claimed is:

1. A method for producing chemical products, comprising:
transporting a first fluid comprising a first chemical reactant through a first module comprising a chemical reactor and at least a second unit operation fluidically connected in parallel, and through a second module connected to the first module in series, the second module comprising at least one separator and at least a fourth unit operation fluidically connected in parallel, such that the first chemical reactant within the first fluid is reacted to form a first chemical product that is transported out of the second module; and
subsequently, transporting a second fluid comprising a second chemical reactant through the first module and the second module such that the second chemical reactant within the second fluid is reacted to form a second chemical product, without forming the first chemical product, such that the second chemical product is transported out of the second module;
wherein:
no additional unit operations are newly fluidically connected to the first and second modules between the steps of transporting the first fluid and transporting the second fluid, and
no unit operations are fluidically disconnected from the first and second modules between the steps of transporting the first fluid and transporting the second fluid.

2. The method of claim 1 , further comprising transporting the first fluid through the at least one separator and separating the first fluid into a first stream containing the first chemical product and a second stream containing a first chemical byproduct.

3. The method of claim 1 , wherein the first and/or second chemical products is an active pharmaceutical ingredient (API).

4. The method of claim 3 , wherein the API is diphenhydramine, lidocaine, diazepam, or fluoxetine.

5. The method of claim 3 , wherein the API is processed downstream into a tablet, a pill, or a liquid.

6. The method of claim 3 , wherein the first and/or second chemical product contains at least about 2.5 mg of the API per milliliter suspended in a pharmaceutically acceptable carrier.

7. The method of claim 1 , wherein the reactor has a volume of less than or equal to about 1 L.

8. The method of claim 1 , wherein the reactor is operated at a pressure of greater than or equal to about 200 psi.

9. The method of claim 1 , wherein the reactor is operated at a temperature of greater than or equal to about 60° C.

10. The method of claim 1 , further comprising, after transporting the first chemical product out of the second module and before transporting the second chemical product out of the second module, rerouting existing fluidic connections between the first module and the second module via a manifold fluidically connected to the first module and the second module.

11. A method for the continuous production of an ingestible pharmaceutical composition within a reactor system, comprising:
transporting an input fluid comprising a chemical reactant through a reactor such that the chemical reactant is reacted, within the reactor, to produce an active pharmaceutical ingredient within a reactor output stream;
transporting the reactor output stream to a separator and separating at least a portion of the active pharmaceutical ingredient from at least a portion of another component of the reactor output stream to produce a separator product stream having a higher concentration of the active pharmaceutical ingredient than the reactor output stream; and
transporting the separator product stream from the separator to a formulator in which the active pharmaceutical ingredient is converted into the ingestible pharmaceutical composition,
wherein the amount of the active pharmaceutical ingredient within the ingestible pharmaceutical composition that is output from the formulator is output at a rate of at least about 20 grams/day, and
wherein the reactor system, including the reactor, the separator, and the formulator, are contained within a housing occupying a volume of less than about 100 ft 3 and/or occupying a footprint of less than about 10 ft 2 .

12. The method of claim 11 , wherein the housing occupies a footprint of less than about 10 ft 2 .

13. The method of claim 11 , wherein the housing occupies a volume of less than about 100 ft 3 .

14. The method of claim 11 , wherein the active pharmaceutical ingredient is diphenhydramine, lidocaine, diazepam, or fluoxetine.

15. The method of claim 11 , wherein the ingestible pharmaceutical composition is a tablet, a pill, or a liquid.

16. The method of claim 11 , wherein the reactor has a volume of less than or equal to about 1 L.

17. The method of claim 11 , wherein the reactor is operated at a pressure of greater than or equal to about 200 psi.

18. The method of claim 11 , wherein the reactor is operated at a temperature of greater than or equal to about 60° C.

19. The method of claim 11 , wherein the formulator comprises a precipitator, a filter, and/or a dissolution tank.

20. The method of claim 11 , wherein converting the active pharmaceutical ingredient into the ingestible pharmaceutical composition comprises:
precipitating the active pharmaceutical ingredient from a solution comprising the active pharmaceutical ingredient and a pharmaceutically acceptable solvent, and/or crystallizing the active pharmaceutical ingredient from a solution comprising the active pharmaceutical ingredient and a pharmaceutically acceptable solvent, and/or
diluting the active pharmaceutical ingredient with a pharmaceutically acceptable solvent.

21. The method of claim 11 , wherein the reactor output stream and/or separator product stream is transported without a pump.

Assignees

• Massachusetts Inst Technology

Inventors

• Jensen Klavs F
• Jamison Timothy F
• Myerson Allan S
• Monbaliu Jean-Christophe M
• Behnam Mohsen
• Wong Shin Yee
• Weeranoppanant Nopphon
• Revalor Eve Marie
• Stelzer Torsten
• Chen Jie
• Adamo Andrea
• Snead David R
• Zhang Ping

Classifications

• B01J2219/00907

  using membranes · CPC title

• B01J2219/00835

  Comprising catalytically active material · CPC title

• B01J19/18

  Stationary reactors having moving elements inside (B01J19/08, B01J19/26 take precedence) · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title

• A61K31/14

  Quaternary ammonium compounds, e.g. edrophonium, choline (betaines A61K31/205) · CPC title