PHARMACEUTICALS
Since the commercial processes are lab-centric and speed to market dictates commercialisation , there is generally no or minimal attempt to minimise solvent use by evaluating and / or creating an alternate optimum process . In pharma , regulations mean that this cannot happen .
Process-centric design / Creativity & imagination
Since most chemists and chemical engineers might not have the feel for chemical interactions , it can be a challenge to incorporate their nuances in actual designs . The unavailability of this data and other properties may mean that they will have to be generated internally . ‘ Skunk works ’ may be needed . This may be a place to experiment with alternative equipment and designs . 12
My experience is that processcentric designs can and do minimise solvent use . Creativity and imagination with these designs go hand in hand here . Downsizing equipment should not change process chemistry but it can change how the chemistry is practised .
Such equipment is used in chemical and other manufacturing industries and reduces solvent use per kilo from the current reactor designs . Many might say that it cannot be done , but unless we consider such outlier / nondestructive creative designs , net zero will not be achieved .
For example , most solid raw materials are fed into a reactor that has a large ( up to 50 %) excess of solvent . However , if the solid can be metered to the reaction system via
Figure 2 - Gravity-based decanter design
Mixed feed an eductor with the solvent , one can reduce the total solvent required , especially if a back-mix flow process design ( Figure 1 ) can be used . 13
Such reaction designs , along with an inline heater or heat exchanger , can reduce solvent use . Plate and frame heat exchangers have been used as reactors . 11 It is critical for chemists and chemical engineers to have a complete understanding and command of the reaction kinetics . 8 Depending on the melting point and solubility of chemicals , there are many opportunities to reduce solvent use . 4 - 6 As stated earlier , insolubility and density differences can be used in many ways to facilitate and simplify processes . 8 , 11 A decanter based on use of density differences is an excellent example ( Figure 2 ). There are many existing examples where solvent use can be significantly reduced or eliminated . 4 - 7 , 14 - 18
One of the reasons for not incorporating many of such nuances in process design is the time pressure to get the product to the market . Almost every chemical synthesis patent shows us the pathway ( reaction mechanism ) to minimise solvent use . However , they are not capitalised on and the laboratory processes are fitted in the existing equipment at the site , which is the proverbial ‘ square plug in a round hole ’. 18
No jacket required
The chemical industry is attuned to using jacketed reactors for chemical synthesis . Most overlook how to exploit the reaction sequencing , kinetics and sociochemicology of
Light liquid
Heavy liquid the chemicals used and produced and the opportunity to reduce solvent is lost .
The equipment used in other industries or used differently in the chemical industry can reduce solvent use and facilitate the processes . ‘ What if ’ comparison analysis is necessary to select the best equipment to do this . 4 - 6 , 12
At times , the best equipment may not be the normal agitated reactor . Inline heaters are all-electric : they not only minimise investment in external heat sources but facilitate capitalising on solubility and reaction kinetics , thereby reducing solvent use for every reaction step . 4 - 6 , 8 This value needs to capitalised on if we want to reduce solvent use .
For example , compared to jacketed reactors inline electrically heated heat exchangers offer much higher heat input ( flux ) per unit surface area , which improves reaction time . Their use as chemical reaction equipment is not publicised and is seldom considered . Capital investment for electrically heated heat exchangers is lower than for Dowtherm or hot oilbased heaters . 12
Chemical reactivity and behaviour has been used in chemical synthesis for more than 60 years , with excellent results . 4 - 6 , 12 Generally they are used in a back-flow mix reactor configuration ; the chemistry in Figure 3 is an excellent example . 13
In the reaction , excessive amount of acetic acid is used as a solvent for 4-bromo-2-chloroaniline . However molten bromochloroaniline can be tested , eliminating the need for acetic acid . Such experiments cannot be tested in the glassware available in the laboratory . The ‘ village team ’ will have to experiment with alternative equipment to test feasibility . Due to its proprietary nature options are not discussed here .
Such designs are subject to IP protection , however . Process designers will be challenged because information is not available
26 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981