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US-20260125493-A1 - SYSTEMS AND METHODS FOR MANUFACTURING HYDROXYPROPYL-BETA-CYCLODEXTRIN

US20260125493A1US 20260125493 A1US20260125493 A1US 20260125493A1US-20260125493-A1

Abstract

Provided herein are systems and methods for manufacturing hydroxypropyl-β-cyclodextrin.

Inventors

  • Steven Pfeiffer
  • Benjamin RIZKIN

Assignees

  • BEREN THERAPEUTICS P.B.C.

Dates

Publication Date
20260507
Application Date
20230613

Claims (20)

  1. 1 . A hydroxypropyl-β-cyclodextrin (HPBCD) reactor system comprising: (a) a propylene oxide feed; (b) a β-cyclodextrin feed; (c) a mass flow meter or controller; and (d) a static mixer.
  2. 2 . The reactor system of claim 1 , wherein the propylene oxide feed is pressurized.
  3. 3 . The reactor system of claim 1 , wherein the β-cyclodextrin feed is pressurized.
  4. 4 . The reactor system of claim 1 , comprising at least two propylene oxide feeds.
  5. 5 . The reactor system of claim 4 , wherein the at least two propylene oxide feeds are operably connected to a separate mass flow meter or controller.
  6. 6 . The reactor system of claim 1 , further comprising a back pressure regulator.
  7. 7 .- 8 . (canceled)
  8. 9 . The reactor system of claim 1 , wherein the β-cyclodextrin feed comprises NaOH.
  9. 10 . The reactor system of claim 1 , wherein the static mixer is a helical static mixer.
  10. 11 . The reactor system of claim 1 , wherein one or more of the feeds is operably connected to a syringe pump.
  11. 12 . The reactor system of claim 1 , further comprising a coil of tubing.
  12. 13 . The reactor system of claim 1 , further comprising a plug flow reactor.
  13. 14 . The reactor system of claim 13 , wherein the plug flow reactor comprises at least two coils of tubing and a temperature control unit.
  14. 15 . The reactor system of claim 1 , wherein the propylene oxide is dosed in at least two places.
  15. 16 . The reactor system of claim 13 , wherein at least one dose of propylene oxide is dosed before the plug flow reactor.
  16. 17 . The reactor system of claim 14 , wherein at least one dose of propylene oxide is dosed before the first coil tubing and at least another dose of propylene oxide is dosed before the second coil tubing.
  17. 18 . The reactor system of claim 6 , wherein the back pressure regulator is operably connected to a plug flow reactor or a coil of tubing.
  18. 19 . (canceled)
  19. 20 . The reactor system of claim 191 , further comprising a collection tank, wherein the collection tank is operably connected to an acid feed.
  20. 21 . The reactor system of claim 1 , further comprising a temperature control unit, wherein the temperature control unit maintains a temperature from about 30° C. to about 60° C.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a 371 application claiming priority to PCT/IB2023/056096 titled “SYSTEMS AND METHODS FOR MANUFACTURING HYDROXYPROPYL-BETA-CYCLODEXTRIN,” filed Jun. 13, 2023, which claims priority to U.S. Provisional Application No. 63/351,719 entitled “SYSTEMS AND METHODS FOR MANUFACTURING HYDROXYPROPYL-BETA-CYCLODEXTRIN” filed Jun. 13, 2022, the entire contents of which are incorporated by reference herein. SEQUENCE LISTING The present application contains a Sequence Listing which has been submitted electronically in .XML format and is hereby incorporated by reference in its entirety. Said computer readable file was created on Nov. 3, 2025, is named “P085960WO-Sequence-Listing.xml” and is 77,607 bytes in size. FIELD The present disclosure relates to systems and methods for manufacturing hydroxypropyl-β-cyclodextrin. Therefore, the disclosure generally relates to the fields of chemistry, pharmacy, and chemical engineering. BACKGROUND Hydroxypropyl-β-cyclodextrin (HPBCD) is of growing interest in the pharmaceutical field for its potential to treat multiple disease types. New systems and methods for producing HPBCD are therefore needed to meet growing demand. SUMMARY OF THE DISCLOSURE Provided herein is a reactor system for producing hydroxypropyl-β-cyclodextrin (HPBCD). The system comprises a propylene oxide feed, a β-cyclodextrin (BCD) feed, a mass flow meter or mass flow controller, and a static mixer. In some embodiments, the system further comprises a back pressure regulator. In some additional embodiments, the system comprises a mass flow controller. In still further embodiments, the system comprises a temperature controller. In some aspects, the static mixer is a helical static mixer. In some embodiments, the propylene oxide feed is pressurized. In other embodiments, the BCD feed is pressurized. In some embodiments, the system comprises at least two propylene oxide feeds. In some aspects, the at least two propylene oxide feeds are operably connected to a separate mass flow meter or controller. In some embodiments, a first propylene oxide feed provides a concentration from about 7 to about 15 equivalents of BCD and a second propylene oxide feed provides a concentration from about 3.5 to about 15 equivalents of BCD. In some embodiments, the BCD feed comprises sodium hydroxide (NaOH). In some aspects, the β-cyclodextrin feed comprises a concentration from about 5 to about 10 equivalents of NaOH. In some embodiments, the system further comprises a pump. In some aspects, the pump may be a syringe pump operably connected to one or more of the feeds. In some embodiments, the system further comprises a coil of tubing. In some embodiments, the system comprises a plug flow reactor. In some aspects, the plug flow reactor comprises at least two coils of tubing and a temperature control unit. In some embodiments, a back pressure regulator is operably connected to a plug flow reactor or a coil of tubing. In some aspects, the temperature control unit maintains a temperature from about 30° C. to about 60° C. In some embodiments, the propylene oxide is dosed in two places. In some aspects, the propylene oxide is dosed before a plug flow reactor. In some additional aspects, at least one dose of propylene oxide is dosed before a first coil of tubing, and at least another dose of propylene oxide is dosed before the second coil of tubing. In some embodiments, the system further comprises a collection tank. In some aspects, the collection tank is operably connected to an acid feed. In some further aspects, the acid feed comprises hydrochloric acid, sulfuric acid, lactic acid, acetic acid, formic acid, citric acid, oxalic acid, uric acid, malic acid, fumaric acid, tartaric acid, or a combination thereof. In some additional aspects, the system provides a total residence time from about 30 minutes to about 70 minutes. Further provided herein is a method of manufacturing a hydroxypropyl-β-cyclodextrin (HPBCD) mixture comprising: (a) contacting a hydroxypropyl-β-cyclodextrin (HPBCD) mixture with at least two solvents, the HPBCD mixture comprising high degree substitution HPBCD and low degree substitution HPBCD; (b) dissolving the high degree substitution HPBCD in one of the solvents; and, (c) removing the low degree substitution HPBCD by precipitation. In some embodiments, the at least two solvents comprise ethanol and acetone. Further provided herein is a method of manufacturing a hydroxypropyl-β-cyclodextrin (HPBCD) mixture comprising: (a) contacting a hydroxypropyl-β-cyclodextrin (HPBCD) mixture with at least two solvents, the HPBCD mixture comprising high degree substitution HPBCD; (b) dissolving the high degree substitution HPBCD in one of the solvents to form a mother liquor; and (c) filtering off the mother liquor. In some embodiments, the method comprises lyophilizing the mother liquor to yield a solid. In some aspects, the method further comprises analyzing the solid by MALDI-