Recent advances in pharmaceutical manufacturing techniques are showing the promise of continuous production, and pharmaceutical firms, currently reliant on mature batch technology, are beginning to turn toward Continuous Pharmaceutical Manufacturing (CPM). Continuous production techniques have efficiency, cost, reliability and quality advantages: in this paper we evaluate and quantify these for the case of the CPM of artemisinin, a key antimalarial Active Pharmaceutical Ingredient (API). Published reaction and unit operation data are analysed, static models developed, and continuous plug flow reactors designed for a reference case producing 100 kg of API per year: the small reactor volumes computed (19.72 mL and 78.72 mL) illustrate one benefit of continuous techniques, that of small equipment footprint. In addition, alternative CPM cases are also computed whereby different continuous API recovery operations are evaluated in comparison to the base case; the latter employs a reported batch product recovery. Utilising published solubility data as well as data estimated using the UNIFAC method, systematic evaluation identifies ethanol (EtOH) and ethyl acetate (EtOAc) as good candidate anti-solvents for continuous crystallisation. For the same 100 kg per year production level of API, designs using continuous separation techniques can achieve significantly improved E-factor values (22.52 average) compared to the batch process (65.28), implying enhanced sustainability through reduced waste generation. This API of critical societal importance is a good candidate for CPM, with the future benefits of performing full analysis and technoeconomic optimisation evident.
- Continuous Pharmaceutical Manufacturing (CPM)
- Green chemistry
- Process design
- Process modelling
- Process simulation