Alan D. Curzons

Expanding GSK's solvent selection guide – embedding sustainability into solvent selection starting at medicinal chemistry

Solvents make a large contribution to the environmental impact of manufacturing processes of active pharmaceutical ingredients (API), as well as playing an important role in other chemical industries, with millions of tons used and disposed of each year. GlaxoSmithKline (GSK) has previously reported on the both the development of a GSK solvent selection guide and the incorporation of solvent life cycle inventory and assessment information. The GSK solvent selection guide has been further enhanced by: • Revising the assessments of factors that impact process safety, separating reactivity from fire and explosion rankings. • More than doubling the number of solvents in the guide, to a total of 110 from the initial 47. • Adding a customised solvent selection guide appropriate for medicinal chemistry and analytical laboratories. The new GSK solvent selection guide enables GSK scientists to objectively assess solvents and determine whether existing or new solvents brought to market as ‘greener’ alternatives truly represent a more sustainable choice or whether they are just addressing a single issue associated with sustainability.

Metrics to ‘green’ chemistry—which are the best?

A considerable amount has been written about the use of metrics to drive business, government and communities towards more sustainable practices. A number of metrics have also been proposed over the past 5–10 years to make chemists aware of the need to change the methods used for chemical syntheses and chemical processes. This paper explores several metrics commonly used by chemists and compares and contrasts these metrics with a new metric known as reaction mass efficiency. The paper also uses an economic analysis of four commercial pharmaceutical processes to understand the relationship between metrics and the most important cost drivers in these processes.

So you think your process is green, how do you know?—Using principles of sustainability to determine what is green–a corporate perspective

An approach to quantitatively and systematically evaluate synthetic organic reactions and processes is described. This sustainability-based approach allows chemists to clearly assess whether or not chemistries and chemical processes are ‘greener’. The results of this work indicate that close attention to effective use and reuse of solvents will result in the largest gains for reducing life cycle impacts in batch chemical operations.

Cradle-to-gate life cycle inventory and assessment of pharmaceutical compounds

Background, Goal and ScopeThe research presented here represents one part of GlaxoSmithKline’s (GSK) efforts to identify and improve the life cycle impact profile of pharmaceutical products. The main goal of this work was to identify and analyze the cradle-to-gate environmental impacts in the synthesis of a typical Active Pharmaceutical Ingredient (API). A cradle-to-gate life cycle assessment of a commercial pharmaceutical product is presented as a case study.MethodsLife cycle inventory data were obtained using a modular gate-to-gate methodology developed in partnership with North Carolina State University (NCSU) while the impact assessment was performed utilizing GSK’s sustainability metrics methodology.Results and DiscussionMajor contributors to the environmental footprint of a typical pharmaceutical product were identified. The results of this study indicate that solvent use accounts for a majority of the potential cradle-to-gate impacts associated with the manufacture of the commercial pharmaceutical product under study. If spent solvent is incinerated instead of recovered the life-cycle profile and impacts are considerably increased.ConclusionsThis case study provided GSK with key insights into the life-cycle impacts of pharmaceutical products. It also helped to establish a well-documented approach to using life cycle within GSK and fostered the development of a practical methodology that is applicable to strategic decision making, internal business processes and other processes and tools.

Green chemistry measures for process research and development

A set of metrics has been developed which enables a simple assessment to be made of batch processes in terms of waste, energy usage, and chemistry efficiency. It is intended to raise awareness of green chemistry by providing a tool to assist chemists in monitoring progress in the reduction of environmental impact as they design new routes and modify processes.

Electrosynthesis of organic compounds

The electrooxidative amination of 1,4-dihydroxybenzene (1) to give 2,5-disubstituted benzoquinones, using dimethylamine, piperidine and morpholine, as nucleophiles has been studied using cyclic voltammetry and controlled potential coulometry. The results indicate that the above-mentioned amines react with electrochemically generated p-benzoquinone via a Michael-addition reaction leading to 2,5-diamino-substituted benzoquinones. Products were obtained in good yield and purity, and were characterized by spectroscopic methods and elemental analysis.Disclosed is a process for the electrochemical transformation of a compound to form a product, the process comprising (i) effecting the transformation in the presence of an electrolyte comprising at least one room temperature ionic liquid, wherein the ionic liquid is air-stable and moisture-stable, (ii) recovering the product, and optionally (iii) recovering the ionic liquid. The process can be used to effect the electrochemical transformation of a wide range of organic compounds.

How do you select the “greenest” technology? Development of guidance for the pharmaceutical industry

There is widespread interest in government and industry in green chemistry and green technology. For truly “green” processes to be developed, scientists must take a concurrent, integrated approach that considers chemistry and technology. While it is vital to understand those things traditionally considered in technology selection such as operational, quality, and cost differences, it is equally vital to understand the associated environmental and safety issues that are inherent to the chosen technology. This is a major challenge and there is a clear need for guidance in this area. This paper proposes the concept of a “Clean/Green Technology Guide” as an expert system that would provide scientists and engineers with comparative environmental and safety performance information on available technologies for commonly performed unit operations in the pharmaceutical industry. At this stage, the framework has been developed to demonstrate the concept, using a metric set based on the concepts of sustainable development. This framework is used to evaluate the alternatives on a case-scenario basis, and will compare traditional and emerging technologies. A life-cycle approach is also used in the evaluation of the alternatives. This approach is illustrated by comparing batch, mini-, and microreactors.

The Pros and Cons of Using Ionic Liquids in the Pharmaceutical Industry

Ionic liquids have the potential to be green alternatives to conventional organic solvents currently utilised by the pharmaceutical industry. However, several factors still have to be addressed before this new technology is unconditionally welcomed by the pharmaceutical industry. Issues encompassing cost, stability, toxicity, ease of processing of pharmaceutical intermediate(s), and advantages over conventional solvents will be addressed in this article.

Chapter 18 Technology assessment for a more sustainable enterprise: The GSK experience

Publisher Summary This chapter discusses the Glaxo Smith Khnes (GSK) experience for technology assessment for a more sustainable enterprise. One aspect of GSK Environment, Health and Safety (EHS) vision for environmental sustainability is to champion the research and implementation of increasingly sustainable technologies and processes. While developing and implementing these programs, it became increasingly clear that the greatest short to medium term gains toward more sustainable practices would be realized at the interface of chemistry and technology. While GSK Corporate EHS had developed considerable understanding of fundamental pharmaceutical industry chemistry and chemical processing approaches to more sustainable practices, there was a lack of understanding about the materials and energy efficiency implications related to technology selection. As a result, a Green Technology Guide (GTG) is developed for technologies and unit operations of interest to the pharmaceutical industry. The Guide is developed as a module of the existing Web-based Green Chemistry Guide, and was designed to provide scientists and engineers with comparative assessments of unit operations from a sustainability perspective.