Periodic Reporting for period 1 - IMPACTIVE (Innovative Mechanochemical Processes to synthesize green ACTIVE pharmaceutical ingredients.)
Période du rapport: 2022-10-01 au 2024-03-31
The environmental impact of the pharmaceutical industry is a huge problem. The production and use of pharmaceuticals cause high CO2 emissions (52 Mtons in 2015, which is more than the automotive industry), contamination of soils, biota, and water, and even dangers to human health through carcinogenic impurities. Although there have been efforts to reduce the environmental impact of active pharmaceutical ingredient (API) production, the use of organic solvents (responsible for 75% of energy used) is still a critical step in many processes. Clearly, new methods to produce pharmaceuticals in a green, efficient, and economically friendly way are required. The IMPACTIVE project brings together the expertise and knowledge from two COST Actions and develops novel green methods to produce active pharmaceutical ingredients (APIs) using mechanochemistry as a disruptive technology. Mechanochemistry uses mechanical processes, such as ball milling, twin-screw extrusion, resonant acoustic mixing, and spray drying, to induce chemical reactions. Mechanochemistry is a solvent-free, highly efficient, environmentally friendly, and affordable disruptive technology to produce APIs. Mechanochemistry has been successfully adopted in other industries already, including aerospace, cosmetics, biomass transformation and agro-foods. Now we propose to validate its use for API manufacturing, which is the goal of the IMPACTIVE project. To do this, we will use mechanochemistry to synthesise APIs of three types: antidiabetics, anticancer and antihypertensives. The results of the IMPACTIVE project will thus enable pharmaceutical manufacturers to move back to Europe while minimizing environmental pollution. Through our strong dissemination and communication strategy we will ensure that the project’s results are shared with scientists, the pharmaceutical industry, and stakeholders from regulatory and public authorities to achieve maximum impact.
During the first stage of IMPACTIVE produced 5 publications focusing in the mechanochemical processes and synthesis of selected active pharmaceutical ingredients (APIs) and their key intermediates, altogether currently marketed as crucial for treating several diseases such as cancer. The traditional solvent-based approaches have been taken as starting points, and alternative mechanochemical processes in the absence of solvents have been investigated, leading to the development of several key transformations with different degrees of advancements, depending on the complexity of the targeted scaffold. For each of these API’s, the potential mechanochemical alternatives have been identified. These have now been partly explored, tested and optimized. In the reporting period, the IMPACTIVE consortium has made the first investigations in replacing at least one solvent-based step in the synthesis of 6 APIs from four different compound families by a mechanochemical alternative at a laboratory scale, both in batch and in continuous. Due to the sensitive information contained in the exploitation strategy, we cannot include the structure of the Active Pharmaceutical Ingredients (APIs) or their key intermediates (KIs) in this summary. For the anticancer drugs APIs, two mechanochemical synthetic strategies are currently ongoing and significative progress has been obtained joining the efforts of the different partners of the Consortium. For some of the compounds within these families, a continuous process is under investigation. All the syntheses developed by a mechanochemical approach overcome frequent problems encountered in solution-based chemistry such as s high catalyst loading and long reaction times, generation less waste than conventional processes in solution. The mechanochemical preparation of APIs belonging to the fourth family of target compounds is still in an exploratory phase. The results will be presented in due course.
By achieving the objectives of the IMPACTIVE project and showing that mechanochemistry is a green, efficient, and affordable alternative to current API manufacturing methods, we will reduce environmental pollution, as well as the EU economy and supply chain stability. Recent data published by the consortium members showed that switching to mechanochemistry to produce a single API (among those listed World Health Organisation, WHO essential medicines) can reduce ecotoxicity and CO2 emissions by more than 85%, while also reducing the production costs by 12%. The use of mechanochemistry would, therefore, overcome some issues encountered in the solvent-based manufacturing through the provision of benefits such as: 1) solvent-free (or minimum solvent use) conditions, 2) safer reaction conditions, 3) efficiency enhancement, 4) lower costs, 5) CO2 emission reduction, and 6) Innovation in chemical space and process engineering.
The results of the IMPACTIVE project will thus enable pharmaceutical manufacturers to move back to Europe while minimizing environmental pollution. Through our strong dissemination and communication strategy we will ensure that the project results are shared with scientists, the pharmaceutical industry, and stakeholders from regulatory and public authorities to achieve maximum impact.
The results of the IMPACTIVE project will thus enable pharmaceutical manufacturers to move back to Europe while minimizing environmental pollution. Through our strong dissemination and communication strategy we will ensure that the project results are shared with scientists, the pharmaceutical industry, and stakeholders from regulatory and public authorities to achieve maximum impact.