Continuous Processing in the Pharmaceutical Industry

Abstract

IntroductionAs the fi ne chemical and pharmaceutical industries progress into the 21st century there is an ever -increasing necessity to improve the sustainability of their manufacturing processes. In 2006 James Clark stated ' The three cornerstones of sustainable development -economic, environmental, and social benefi t -each provide drivers for change that should help to push the application of green chemistry forward ' [1] . The responsibility, therefore, is on the manufacturer to develop and operate sustainable processes, for example, by (i) reducing waste or treating waste to render it nonhazardous. (ii) improving process effi ciency by using less raw materials and by recycling and re -using solvents whenever appropriate, and (iii) developing cleaner, more energy -effi cient processes and by reducing emissions through effective abatement management.One useful measure of a process ' s sustainability is the E factor [2] . As defi ned by Roger Sheldon, the E factor is the ratio (by weight) of the by -products to the desired product(s). The pharmaceutical and fi ne chemical industries routinely operate processes with E factors one to two orders of magnitude higher than their petrochemical counterparts. There are many reasons for this, including the high level of chemical complexity in pharmaceutical products and the high quality standards in the pharmaceutical industry, but another circumstance contributing to this difference between the E factors is the type of manufacturing technology employed. The petrochemical industry tends to operate continuous processes, whereas the fi ne chemical and pharmaceutical industries predominantly use less effi cient batch manufacturing methods. It could be argued that the different production techniques simply refl ect the volume and complexity of the materials manufactured. Is it correct, however, that relatively simple petrochemical products are produced using modern continuous -based manufacturing technologies whereas pharmaceutical products and intermediates are produced using older batch methods?In the fi eld of organic chemistry, new synthetic strategies and methodologies are developed at an astonishing rate to access a diverse range of molecules.

Development of an Intermittent-Flow Enantioselective Aza-Henry Reaction Using an Arylnitromethane and Homogeneous Brønsted Acid–Base Catalyst with Recycle

“…The two main types of continuous reactors are plug flow reactors (PFRs) and continuous stirred tanks (CSTRs) . Neither one of these truly continuous reactor types is ideally suited for the aza-Henry reaction targeted here.…”

Microscale technology and biocatalytic processes: opportunities and challenges for synthesis

“…Table 3. Benefits of implementation of enzymatic microreactors using non-aqueous media for bioprocess intensification and development [27] Biocatalyst format and reaction medium Challenges in microreactor technology for manufacturing The move from traditional batch reactors to continuous-flow processes in industrial manufacturing remains slow due to several perceived barriers [16,77,78]. Standardized reactor modules that can be combined in various sequences to test novel biocatalytic processes are crucial for rapid development.…”

“…The environmental impact could be significantly improved by using microfluidic devices offering better selectivity and yield and fewer byproducts. The type of manufacturing technology employed contributes to the lower amount of waste produced per amount of product for a petrochemical compared with products in the pharmaceutical/fine chemical industries [16]. The dimension-dependent benefits apply equally well to bioprocesses (e.g., enzymatic cyanohydrin synthesis) where smaller reaction volumes translate into smaller amounts of hydrogen cyanide (HCN) and hence improved safety with fewer risks [17].…”

Life cycle analysis of solvent reduction in pharmaceutical synthesis using continuous adsorption for palladium removal

“…Although several success stories have been documented, there is still great potential to further this approach. [10] Application of the 12 Principles of Green Chemistry related to minimizing the use of solvents and other raw materials, energy usage and their associated life cycle impact are described in this paper related to Heck coupling reactions, common to API synthesis. [11] Heck couplings are one of several types of chemical reactions used in the pharmaceutical industry to produce Downloaded by [Michigan State University] at 11:53 18 February 2015 complex intermediates and active pharmaceutical ingredients (API).…”