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A system view of solvent selection in the pharmaceutical industry: towards a sustainable choice

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Abstract

This paper presents a review of approaches that may be useful for the selection of solvents in the early stages of process development for the synthesis of active pharmaceutical ingredients. Characteristics of the methodologies and their applicability in early stages are explored. Early stages of development are recognised as ideal for detecting benefits and issues regarding the use of solvents. The “system” concept is introduced for the evaluation and selection of solvents in pharmaceutical processes; this concept does not yet seem to be widely utilised within the fine chemicals and pharmaceutical industries. System analysis is considered an important tool for viewing solvent selection from a holistic perspective. Hence, approaches suitable for the early stages of development and considering a holistic perspective might deliver more sustainable processes. The evolution of the synthesis of Ibuprofen API is used to illustrate this concept.

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Abbreviations

API:

Active pharmaceutical ingredient

BRITEST:

Best route innovative technology evaluation and selection techniques

CAMD:

Computer-aided molecular design

EFRAT:

Environmental fate and risk assessment

eNRTL-SAC:

Ionic non-random two liquid segment activity coefficient thermodynamic model

FDA:

Food and drug administration

FPP:

Finished pharmaceutical product

GMP:

Good manufacturing practice

HAP:

Hazardous air pollutants

HF:

Anhydrous hydrogen fluoride

HSE:

Health safety and environment

LCA:

Lifecycle assessment

MACT:

Maximum available control technology

MEIM:

Methodology for environmental impact minimisation

MHRA:

Medicine and healthcare products regulation agency

NRTL:

Non-random two liquid thermodynamic model

NRTL-SAC:

Non-random two liquid segment activity coefficient thermodynamic model

RSMs:

Regulatory starting materials

UNIFAC:

Universal Functional Activity coefficient

USEPA:

United States environmental protection agency

VOCs:

Volatile organic compounds

VOE:

Volatile organic emissions

WAR:

Waste reduction algorithm

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Acknowledgments

The author would like to thank the CONACYT for providing the funding for the development of this research project. The author also would like to thank the reviewers and editors of this journal for their feedback in the revision process. We also expressed our acknowledgement to the consortium BRITEST for sharing information regarding current solvent selection in the industry.

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Authors and Affiliations

  1. School of Chemical Science, Autonomous University of Chihuahua, Circuit 1, New University Campus, CP 31125, Chihuahua, Mexico

    S. Perez-Vega, E. Ortega-Rivas & I. Salmeron-Ochoa

  2. Institute of Chemical and Engineering Sciences, Jurong Island, 627833, Singapore

    P. N. Sharratt

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  1. S. Perez-Vega
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  2. E. Ortega-Rivas
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  3. I. Salmeron-Ochoa
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  4. P. N. Sharratt
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Correspondence to S. Perez-Vega.

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Perez-Vega, S., Ortega-Rivas, E., Salmeron-Ochoa, I. et al. A system view of solvent selection in the pharmaceutical industry: towards a sustainable choice. Environ Dev Sustain 15, 1–21 (2013). https://doi.org/10.1007/s10668-012-9365-5

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