Process modelling, simulation and technoeconomic evaluation of crystallisation antisolvents for the continuous pharmaceutical manufacturing of rufinamide

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Abstract

Continuous pharmaceutical manufacturing (CPM) is a promising new paradigm to produce active pharmaceutical ingredients (APIs), allowing reduced equipment dimensions, lower waste production and energy consumption, and safer operation in comparison to the industrially dominant batch methods. Rufinamide is an antiepileptic agent whose demonstrated continuous flow synthesis (featuring three reactions in flow) circumvents the accumulation of toxic and explosive organoazide intermediates. To ascertain the feasibility and viability of this continuous synthetic route, systematic process modelling and costing is required. This paper presents a technoeconomic analysis of the upstream continuous flow synthesis of rufinamide via steady-state process modelling and plantwide simulation. Reaction kinetics and Arrhenius parameters are estimated from previously published experimental data, and plug flow reactor (PFR) volumes are calculated towards rigorous plant costing. Continuous reactor and separator units have been designed, and the CPM flowsheet is compared vs. the batch production method, with respect to technical efficiency and profitability. Plantwide costing via an established economic analysis methodology has been pursued to enable a detailed comparison of cost items towards process scale up,
as well as motivate the need for further systematic optimisation.
Original languageEnglish
JournalComputers and Chemical Engineering
Early online date28 Dec 2017
DOIs
Publication statusE-pub ahead of print - 28 Dec 2017

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