SBIR-STTR Award

Continuous liquid-liquid extractors for doubling of productivity and henhancement of batch based drug manufacturing
Award last edited on: 2/17/2024

Sponsored Program
SBIR
Awarding Agency
NIH : NIGMS
Total Award Amount
$1,747,335
Award Phase
2
Solicitation Topic Code
859
Principal Investigator
Andrea Adamo

Company Information

Zaiput Flow Technologies LLC

4 Gordon Place
Cambridge, MA 02139
   (617) 714-9806
   617-714-9806
   www.zaiput.com
Location: Single
Congr. District: 07
County: Middlesex

Phase I

Contract Number: 1R43GM140701-01
Start Date: 5/1/2021    Completed: 3/31/2022
Phase I year
2021
Phase I Amount
$247,065
Domestic pharmaceutical manufacturing is struggling to meet demands. It is therefore imperative to develop tools to rapidly increase the productivity of existing production plants. Manufacturing of pharmaceuticals currently relies almost entirely on batch-based chemical synthesis. In this approach, chemical synthesis takes place in several separate steps within large reactors. Synthesis in continuous flow (with chemicals flowing continuously during the reaction process) is emerging as a more efficient alternative. However, synthesis in continuous flow is not being widely adopted due to several practical reasons, including the need for major investments to overhaul existing production plants. Liquid-liquid extraction (LLE) represents the most frequent post-reaction step in pharmaceutical syntheses. Importantly, while technologies currently used for LLE in the context of batch synthesis are a bottleneck that dramatically reduces process efficiency, LLE extraction in continuous flow is highly efficient. Existing technologies for LLE in flow cannot currently be used in batch-based manufacturing plants because their maximum flow rate is too low to meet the demands of batch-based production plants. Here, we propose to develop a novel, high capacity system to implement LLE in continuous flow in the context of batch-based pharmaceutical synthesis. We envision a plug and play, portable, high flow rate, self-tuning device deployable in existing pharmaceutical production plants without the need to overhaul production processes. To build this system, in the Phase I of this SBIR, we will address the key technological innovations needed to build a self-standing, high capacity continuous LLE system compatible with large-scale batch-based pharmaceutical production. Namely, we will: 1) develop a continuous flow liquid-liquid extraction system able to handle high (turbulent) flow rates and 2) we will develop a self-tunable pressure control system able to support the operation of such a device with minimal external control. In the Phase II of this SBIR, we will take advantage of these technological innovations to create a user-friendly product ready for deployment within existing pharmaceutical production plants. If successful, this project will produce a tool able to immediately increase the productivity of existing pharmaceutical plants from 2 to 5-fold. This product will redefine the landscape of pharmaceutical production in the United States and beyond.

Public Health Relevance Statement:
Project Narrative Current pharmaceutical manufacturing is struggling to meet demands. A major bottleneck of modern pharmaceutical production is liquid-liquid extraction. Here, we propose the development of a new tool for liquid-liquid extraction that is expected to swiftly increase the productivity of existing pharmaceutical manufacturing plants 2 to 5-fold without the need for process overhaul.

Project Terms:
chemical synthesis; Chemistry; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Emulsions; Experimental Designs; Goals; Hybrids; Investments; Lead; Pb element; heavy metal Pb; heavy metal lead; Methods; Modernization; Plants; Play; pressure; Production; Productivity; Sales; Technology; Testing; Time; United States; Water; Hydrogen Oxide; ethyl acetate; base; improved; Phase; Chemicals; Logistics; fluid; liquid; Liquid substance; tool; Adopted; Reaction; Techniques; System; membrane structure; Membrane; Hydrophobicity; hydrophilicity; novel; Amendment; technological innovation; Devices; Property; portability; drug production; Manufacturer; Manufacturer Name; Drops; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; Pharmacologic Substance; small molecule; Address; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Process; Development; developmental; cost; design; designing; novel strategies; new approaches; novel approaches; novel strategy; Outcome; manufacturing process; scale up; user-friendly; commercialization; real world application; flexibility; flexible; operation

Phase II

Contract Number: 2R44GM140701-02
Start Date: 5/1/2021    Completed: 12/31/2023
Phase II year
2022
(last award dollars: 2023)
Phase II Amount
$1,500,270

Domestic pharmaceutical manufacturing is struggling to meet demands. It is therefore imperative to develop tools to rapidly increase the productivity of existing production plants. Manufacturing of pharmaceuticals currently relies almost entirely on batch-based chemical synthesis. In this approach, chemical synthesis takes place in several separate steps within large reactors. Synthesis in continuous flow (with chemicals flowing continuously during the reaction process) is emerging as a more efficient alternative. However, synthesis in continuous flow is not being widely adopted due to several practical reasons, including the need for major investments to overhaul existing production plants. Liquid-liquid extraction (LLE) represents the most frequent post-reaction step in pharmaceutical syntheses. Importantly, while technologies currently used for LLE in the context of batch synthesis are a bottleneck that dramatically reduces process efficiency, LLE extraction in continuous flow is highly efficient. Existing technologies for LLE in flow cannot currently be used in batch-based manufacturing plants because their maximum flow rate is too low to meet the demands of batch-based production plants. Here, we propose to develop a novel, high capacity system to implement LLE in continuous flow in the context of batch-based pharmaceutical synthesis. We envision a plug and play, portable, high flow rate, self-tuning device deployable in existing pharmaceutical production plants without the need to overhaul production processes. To build this system, in the Phase I of this SBIR, we have addressed the key technological innovations needed to enable the proposed innovation. In Phase II we are planning to demonstrated scalability of the Phase I findings; develop a suitable packaging approach for low cost, chemically resistant separation modules; build and test in a plant facility a complete, user-friendly high capacity continuous LLE system compatible with large-scale batch-based pharmaceutical production. If successful, this project will produce a tool able to immediately increase the productivity of existing pharmaceutical plants from 2 to 5-fold. This product will redefine the landscape of pharmaceutical production in the United States and beyond.

Public Health Relevance Statement:
Project Narrative Current pharmaceutical manufacturing is struggling to meet demands. A major bottleneck of modern pharmaceutical production is liquid-liquid extraction. Here, we propose the development of a new tool for liquid-liquid extraction that is expected to swiftly increase the productivity of existing pharmaceutical manufacturing plants 2 to 5-fold without the need for process overhaul.

Project Terms:
Modification; Development; developmental; cost; design; designing; novel strategies; new approaches; novel approaches; novel strategy; manufacturing process; manufacturing facility; scale up; innovation; innovate; innovative; Resistance; resistant; user-friendly; prototype; commercialization; flexibility; flexible; operation; experimental study; experiment; experimental research; design-build-test; Acetone; 2-Propanone; Dimethyl formaldehyde; chemical synthesis; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Experimental Designs; Goals; Grant; Hybrids; Investments; Lasers; Laser Electromagnetic; Laser Radiation; Lead; Pb element; heavy metal Pb; heavy metal lead; Methods; Methodology; Modernization; Plants; Play; pressure; Production; Productivity; social role; Role; Sales; Technology; Tensile Strength; Testing; Time; Toluene; methyl-benzene; United States; Water; Hydrogen Oxide; Work; ethyl acetate; Film; base; improved; Surface; Solid; Phase; Chemicals; Logistics; fluid; liquid; Liquid substance; tool; Adopted; Reaction; Techniques; System; Location; membrane structure; Membrane; Hydrophobicity; hydrophilicity; novel; Amendment; technological innovation; Devices; Property; portability; drug production; Manufacturer Name; Manufacturer; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; Pharmacologic Substance; small molecule; Address; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Process