PHARMACEUTICALS
solvent. This led to a 20 % lower E-factor( counting water as waste) and a 40 % cut in CO 2 emissions from solvent reduction. Milder conditions also improved robustness, product purity and reduced energy needs.
This achievement extends beyond the laboratory and shows strong potential for manufacturing. It is noteworthy that reactions based on micellar solutions exhibit more pronounced differences at larger scales, especially when compared with reactions based on organic solvents. Therefore, a dedicated scale-up programme was executed, employing methodologies specifically tailored to address the distinctive challenges of micellar chemistry.
The new process offers clear environmental and economic benefits, including lower carbon emissions, reduced waste, improved safety and significant cost savings, despite the unavoidable use of a costly building block. Reusing mother liquors after filtration further cuts waste and lowers API manufacturing costs. Unlike most new technologies, micellar chemistry requires no new equipment, as it works with existing assets.
All of this contributes to more sustainable processes and more affordable medicines, including those based on peptides. Interestingly, the amount of water used by this new chemistry is not necessarily larger than in classical chemistry as operations such as extractions with water during work-ups can be simplified in many cases.
Hovione is deeply involved in this new chemistry with its own research programme, as well as in collaborations to expand its technology platforms to build a more sustainable industry. The company is investing in both new assets and innovative technologies to meet customer demand for more sustainable integrated and differentiated development and manufacturing services in drug substance, particle engineering and drug product.
Conclusions
Although organic solvents will remain in use, water-based methods for organic synthesis are rapidly advancing, offering a shift away from petroleum-based media. Micellar chemistry is a promising, sustainable alternative, combining versatility with environmental and economic benefits. Key advantages include:
• Mild conditions, often at room temperature, which is ideal for sensitive compounds
• Lower catalyst loadings, especially for precious metals, reducing cost and environmental impact
• Less organic solvent use, which reduces solvent usage, cuts waste, simplifies treatment and lowers E-factors
• Recyclable catalysts and surfactants, enhancing sustainability and cost-efficiency
• Improved safety, because it reduces exposure to hazardous solvents and thermal risks. ●
Figure 3 – Surfactants applicable to micellar chemistry
References: 1: D. J. C. Constable, C. Jimenez-Gonzalez & R. K. Henderson, Org. Process Res. Dev., 2007, 11( 1), 133 – 137. 2: Sheldon E-Factor Calculator, Sheldon. nl. 3: B. H. Lipshutz, Curr. Opin. Green Sustain. Chem., 2018, 11, 1 – 8. 4: M. Cortes-Clerget, J. Yu, J. R. A. Kincaid, P. Walde, F. Gallou & B. H. Lipshutz, Chem. Sci., 2021, 12( 12), 4237 – 4266. 5: B. H. Lipshutz, S. Ghorai & M. Cortes-Clerget, Chem. Eur. J., 2018, 24( 26), 6672 – 6695. 6: S. Handa, Y. Wang, F. Gallou & B. H. Lipshutz, Science, 2015, 349( 6252), 1087 – 1090. 7: S. Handa, B. Jin, P. P. Bora, Y. Wang, X. Zhang, F. Gallou, J. Reilly & B. H. Lipshutz, ACS Catal., 2019, 9( 3), 2423 – 2431.
Figure 4 – New step using micellar chemistry
15 % less
Raw materials cost
75 % less
Organic solvents quantity
40 % less
Carbon release
10 2 c less Reaction temperature
Surfactant solution reuse
Safety
Criticality 1 instead of 3
Carlos Alvarez
R & D FELLOW SCIENTIST
HOVIONE k + 351 919071512 J calavarez @ hovione. com j www. hovione. om
24 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981