Digitising chemistry leads to 3D-printed drug factories

Glasgow team encodes synthesis of drug molecules, resulting in portable on-demand apparatus

One of the barriers for the use of many drugs in remote locations is the difficulty of making them. The active ingredients for drugs are complex molecules, and their manufacture is equally complicated; as well as sometimes being hazardous. The Glasgow team, led by Prof Leroy (Lee) Cronin, claims that its discovery might help to change that.

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The Cronin group’s reactionware for making baclofen Lee Cronin/Sergey Zalesskiy

The Cronin Group has for some years been developing what it calls “reactionware”: vessels containing catalysts and other materials that are designed to produce specific chemicals when simple, readily-available starting materials are added. These vessels are designed to be made by 3D printing on low-cost equipment, from cheap materials like polyethylene.

In their latest research, published in Science, the group describes the translation of bench-scale synthesis of drugs ingredients into a digital code which, in turn, “guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations.”

Making good on the concept, the paper describes how Cronin’s team applied their technique to a compound known as baclofen, a muscle relaxant, resulting in printing a set of five interconnected reaction vessels, with up to 32ml capacity, that perform four chemical reactions in 12 steps including filtration and evaporation. Other reactionware produced an anticonvulsant agent and as proton-pump inhibitor, used to counter stomach ulcers.

The vessels were printed on Ultimaker 3D printers, which are commercially available, pausing the programme to drop in components such as magnetic stirrer bars and different types of filter modules. The printing process allowed the incorporation of features like ports to introduce nitrogen and to pump reactants in.

“This approach will allow the on-demand production of chemicals and drugs that are in short supply, hard to make at big facilities, and allow customisation to tailor them to the application,” Cronin told Science.

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The reactionware can be made in a commercially-available 3D printer Lee Cronin/Sergey Zalesskiy

Another advantage is that the reactionware is designed to be used according to a recipe that anyone can follow, meaning that unlike a drug plant, a qualified chemist or engineer does not have to operate the process. “It will allow organic chemists to focus on creating new molecules,” he said.

Cronin envisages the technique making the digitised synthesis into a computer file that can be shared in the same way that digital music and video are now passed around, making compounds that are currently very expensive, or too short-lived to manufacture centrally and distribute, such a radioactively-labelled substances, more readily available to those who need them or want to work with them.

He acknowledges that this might lead to regulatory complications, but believes that the advantages of the technique, particularly in its potential to create new business models, are such that regulators will be keen to find a way to make it work.

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