| Summary: |
In the last decade, economic changes had repercussions in all industries; even the pharmaceutical industry, with its high profits obtained, starts to be pressured from all parts of the pharmaceutical value chain. Shift from the traditional pharmaceutical batch processes to continuous processes starts to be imperative in this new era. The Novartis/MIT protocol and the creation of the new Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC)-UK, involving 7 universities and 30 industries, are examples of the Governments and companies' commitment in this process revolution. In order to obtain continuous manufacturing, research focuses in microreactors, static mixers and oscillatory baffled reactors (OFR), the last being in advantage, due to their good results in mixing intensification and scale-up prediction. In last years a new generation of OFR has been arising, the meso-OFR. These mesoscale (milliliter) oscillatory baffled reactors have received considerable attention due to their small volume and ability to operate at low flow rates, reducing reagent requirements and waste. Based on theoretical and experimental observations a research team, headed by the principal investigator (PI) of the present project, found new dimension ranges and design of the reactor, fulfilling some of the gaps observed in the conventional OFR, as well as in the meso OFR, actually known. Based on this novel OFR a laboratory prototype was built. This apparatus, under evaluation for patent protection [1], has been used in continuous or batch mode for mixing intensification using different multiphase systems. The excellent results obtained attracted the interest of the most important Portuguese pharmaceutical industries, Hovione and Bial, as well as the international companies, Nitech and HELgroup, and the biggest European research center in continuous crystallization, CMAC, being several protocols under evaluation, two of them already signed.
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Summary
In the last decade, economic changes had repercussions in all industries; even the pharmaceutical industry, with its high profits obtained, starts to be pressured from all parts of the pharmaceutical value chain. Shift from the traditional pharmaceutical batch processes to continuous processes starts to be imperative in this new era. The Novartis/MIT protocol and the creation of the new Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC)-UK, involving 7 universities and 30 industries, are examples of the Governments and companies' commitment in this process revolution. In order to obtain continuous manufacturing, research focuses in microreactors, static mixers and oscillatory baffled reactors (OFR), the last being in advantage, due to their good results in mixing intensification and scale-up prediction. In last years a new generation of OFR has been arising, the meso-OFR. These mesoscale (milliliter) oscillatory baffled reactors have received considerable attention due to their small volume and ability to operate at low flow rates, reducing reagent requirements and waste. Based on theoretical and experimental observations a research team, headed by the principal investigator (PI) of the present project, found new dimension ranges and design of the reactor, fulfilling some of the gaps observed in the conventional OFR, as well as in the meso OFR, actually known. Based on this novel OFR a laboratory prototype was built. This apparatus, under evaluation for patent protection [1], has been used in continuous or batch mode for mixing intensification using different multiphase systems. The excellent results obtained attracted the interest of the most important Portuguese pharmaceutical industries, Hovione and Bial, as well as the international companies, Nitech and HELgroup, and the biggest European research center in continuous crystallization, CMAC, being several protocols under evaluation, two of them already signed.
Despite the excellent heat and mass transfer performance observed so far, experimental and theoretical studies need to be continued, especially in what concern to continuous crystallization of active pharmaceutical ingredients (APIs), in order to overcome limitation associated to the technology transfer to the industry, the main goal of the project. By this way, the following studies are planed:
1. Explore flow field and mixing with and without solids;
2. Control nucleation in continuous flow environment to achieve controlled/predictable scale up;
3. Match nucleation/growth with flow conditions to control crystal quality;
4. Scale-up studies
For these developments four research units and one pharmaceutical company (Hovione) will be involved in the project.
The expected shift from batch to continuous manufacturing of the APIs will be a demonstrable example of excellent research contributing to society and to the economy.
The knowhow obtained will support further applications for national and international projects in partnership with the industry, allowing an increase in long-term collaboration. These collaborations are inline with the Health Cluster Portugal objectives, with the FCT recommendations for a sustainable research [2], as well as with the new orientations of Portugal 2020 and Horizon 2020 programs. This proposal will allow the advanced training of human resources by involving PhD and Master students, and support the interaction of these with the industry. |