Abstract

PurposeNovel process windows allow the development of faster, flexible, and greener processes. Therefore, novel process windows were applied to develop a greener process for the synthesis of vitamin D3. In this study the environmental impacts of several batch pathways to obtain vitamin D3 are benchmarked against the continuous microflow process, where novel process windows such as high temperature and pressure were applied. To evaluate the environmental impact of these processes, life cycle assessments were conducted.MethodsA new process concept was developed to optimize and simplify the synthesis of crystalline vitamin D3. This process was conducted in microflow by combining UV photoirradiation and high-p,T (photo-high-p,T) processing. Microreactors allow a high photon flux and enable the harsh conditions, respectively. The process was coupled with an integrated continuous crystallization, and its feasibility has been proven and reported before. The potential environmental impacts were assessed from a cradle-to-gate perspective. Both processes, continuous and batch, were modeled in Aspen Plus using foreground data from the experimental continuous setup, and background data from different patents. The assessment was performed in the software Umberto NXL LCA using the ReCiPe Midpoint 2008 method.Results and discussionThe continuous process has a significantly lower environmental impact than the batch processes. This lower impact is largely due to the fact that fewer amounts of material, particularly solvents, are used. Moreover, the continuous process is faster and has fewer steps, i.e., process-simplified. Among the industrial processes, the synthesis conducted in isopropanol has the lowest environmental impact, although, even in this case, the impact is between 20 and 30 times higher—depending on the conditions—compared with the continuous process. When the batch process is conducted in benzene, the worst environmental impact is obtained. Finally, recycle of the solvent for the best batch case was assessed. This improved the batch process to make it comparable with the continuous process.ConclusionsThe continuous production of vitamin D3 leads to an interesting alternative to the industrial process. Continuous manufacturing of vitamin D3 is faster, requires fewer steps, and uses less solvents compared with the industrial synthesis. However, although the environmental impact of this continuous process is already lower than that of the batch processes, the continuous process can still benefit from further optimization, particularly the introduction of a recycle loops for the solvents methyl tert-butyl ether and acetonitrile.

Highlights

  • Continuous processing has become a hot topic in the pharmaceutical industry because of (i) the increased quality and its reproducibility, (ii) the reduction of safety concerns when using hazardous chemicals and a faster and more predictable scale-up, (iii) the reduction in the size of the factories with increased flexibility and modularity and lower capital costs, (iv) the use of novel process windows and green chemistry to reduce the complexity of multistep

  • In the process of transfer from batch to continuous processing, microreactors have contributed greatly; their use fulfills all the above requirements and enables the possibility to work in harsh conditions, called novel process windows (NPWs) (Hessel et al 2008, 2011)

  • The first section analyzes the flow process with the purpose of finding the areas of improvement, the second section compares the industrial process with the flow process, and the third section explores how the recovery of the solvent reshape the environmental impact of a batch case

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Summary

Introduction

Continuous processing has become a hot topic in the pharmaceutical industry because of (i) the increased quality and its reproducibility, (ii) the reduction of safety concerns when using hazardous chemicals and a faster and more predictable scale-up, (iii) the reduction in the size of the factories with increased flexibility and modularity and lower capital costs, (iv) the use of novel process windows and green chemistry to reduce the complexity of multistepInt J Life Cycle Assess (2019) 24:2111–2127 synthesis, (v) the shorter time-to-market by using modular smart factories, and (vi) overall lower cost and environmental impact (Hempel 2009; Malet-Sanz and Susanne 2012; Sahlodin and Barton 2015; Wegner et al 2012). In the process of transfer from batch to continuous processing, microreactors have contributed greatly; their use fulfills all the above requirements and enables the possibility to work in harsh conditions, called novel process windows (NPWs) (Hessel et al 2008, 2011). Such NPW intensification allows to shorten residence times, increasing the productivity and optimizing the sustainability. The roundtable, motivated by the legislative authority (FDA), has put continuous manufacturing in the top green engineering research areas (Jimenez-Gonzalez et al 2011)

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