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Drug Development

More 3-D Drug Printing Excitement

Chemjobber drew my attention to this a few days ago, rightly noting that someone was indeed falling for a big ol’ pile of hype. There’s an awful lot of breathless stuff out there about “3-D printed drugs”, and this will serve as a fine example. Many of these pieces suffer from one or more of these errors

Confusing a drug with a formulated dose of a drug. That was the case with the press reports back in August. It’s certainly reasonable to imagine spraying down layers of a known drug along with excipients and other formulating agents until you get up to a useful dosage, but too many of these reports seem to think that the “printer” is somehow synthesizing the drug.

Not understanding what organic synthesis is. If you were to design some sort of 3-D printer thingie to make a new compound, how exactly would that work? This confusion was greatly added to by the publicity around the Burke synthesis machine, which (although very interesting) was nothing of the kind. Most reactions need reagents, and most of them need solvents, and many of them need controlled temperatures and other conditions. How is spraying things out of a tiny nozzle going to accomplish all these? The closest thing I can imagine is some kind of flow chemistry reactor whose output (or the output of an associated LC system) is then sort of spray-dried onto a surface. But that process will have to be carefully optimized each time if you’re going to use it, and you’ll have to have a good reason for going to the trouble. The article I’m linking to today slides from formulations to de novo synthesis without even so much as a missed step, but they’re very different things:

The technology could, in theory, allow users to print drugs of any size, shape, and dosage with ease. All they’d need is a downloadable recipe, basically a set of instructions that the printer reads and follows. As long as their home printer is stocked with the necessary base compounds, they could synthesize any and every formulation they’d need. It’d be just like using recipes from a cookbook, only it’d take only half as much work. . .

“The necessary base compounds” – that’s the tricky part. Are those the active drugs themselves? You’re going to keep a whole variety of those around in your Drug-o-matic Printer in case you’re prescribed one of them? How big is this thing supposed to be, anyway?

Overestimating what we know about drug delivery, and how hard it is to know it. This article (as above) blithely talks about whole lists of formulations, tailored to every patient. But the number of formulations for any given drug is often rather shorter than that, and that’s because every time you change one you have to take it into a bunch of patients and carefully make sure that it’s doing what it’s supposed to do. You can, in fact, totally screw up a useful drug’s effects by formulating it wrongly. The time and effort it takes to come up with good formulations means that there’s not going to be some sort of screen with three or four sliders on it, all of which can be varied to make something useful. And I haven’t even gotten into stability, polymorphs, and all the other wonderful things that makes that field such a joy.

15 comments on “More 3-D Drug Printing Excitement”

  1. JM says:

    This reminds me of the silly “Big Pharma Game”. In that game, one discovers new “ingredients” which one can then feed into one’s drug-making assembly line to combine with other “ingredients” to make new drugs. Viola!

    And that’s the *least* wrong part of the game.

    1. dvizard says:

      > This reminds me of the silly “Big Pharma Game”
      I need this game. Sounds like fun 🙂

  2. oldnuke says:

    They have been watching too many old episodes of Star Trek.

  3. ab says:

    I thought this particular article did a reasonable job of remaining within the realm of formulation science, staying away from synthesis. A lay person certainly could get the wrong idea, but that’s true of just about any article about a specialized field. I actually rather like the vision:
    “Pills created to release a cocktail of drugs over definite intervals could wrap up a whole day’s worth of dosage into a single, easy-to-swallow pill. Tell grandpa to toss out that old pill organizer; he’ll get everything he needs from a single tab, no fuss or chance to forget.”
    It’s not a bad idea, really. Grandpa buys bulk supply of 10 API’s and formulates it into a single pill.

    Now, whether we’ll ever realize that vision due to the complex relationship between formulation and individual PK is a different matter. Making a simple fixed dose formulation of just 2 well-known compounds is hard enough. But you’ve gotta respect the vision.

  4. Dilbert says:

    3D printing certainly is exciting.

  5. Alan Blanchard says:

    I actually built a DNA printer 20 years ago as a postdoc in Lee Hood’s lab. Took an Epson printer head and replaced the ink with DNA phosphoramidites dissolved in propylene carbonate and used that to deliver 40pL droplets onto an activated glass surface. I could synthesize 40,000 60-mers on a microscope slide. I guess if you could use tiny amounts of DNA as a drug, you could call that a 3-D drug printer. That technology became the basis for a company called Rosetta Inpharmatics in Seattle. Agilent later bought the rights to the technology and still makes DNA libraries with it.

  6. Tim says:

    Regardless, I would rather think about Chinese traditional medicine. A 3D-printing model would not be a bad idea if the individual patient needs to “cook” his or her herbals to become pill formula, etc. Giving any imagination and creativity, we can see them within next 5 years from now on.

  7. Paul Brookes says:

    I lump this together with the news media hype about Al Qaeda, Isis or whoever using “social media” to plan terrorist attacks, when in-fact it turns out they’re using regular old un-encrypted SMS just like your grandma has on her 15 year old dumb-phone. It just sounds more modern to say it, so they do.

    Same thing with many new technologies – there are those who use it in order to say they’re using it and thus appear cool/modern, versus those cases where there’s actually a demonstrated need or advantage to using the new tech’ versus what was already available.

  8. anon says:

    “publicity around the Burke synthesis machine”

    The article “The End of Synthesis” was among the main reasons for its publicity.

    1. Derek Lowe says:

      But the press releases from Illinois calling it “3D printing” were already out there even before I posted. And I made sure not to call it that, and to disparage the term. . .

  9. building block says:

    it’s only a matter of time until they start 3D printing chemists.

  10. DrugA says:

    Would a machine that makes a sustained release formulation be a 4D printer?

  11. Piotr Nowak says:

    Lee Cronin has been working on 3D printers which can do some real organic synthesis (links below). So in principle it should be possible to use them to ‘print your own drug’. Of course that’s much more complicated than all those overhyped formulations-only drug 3D printing papers. But the purification part still needs to be solved.

    http://www.nature.com/nchem/journal/v4/n5/full/nchem.1313.html
    http://pubs.rsc.org/en/Content/ArticleLanding/2013/SC/C3SC51253C#!divAbstract

  12. André says:

    Thanks, Derek. It may now be time to write a piece on 3-D printed organs…. A further an area of massive 3-D hype.

  13. Rich says:

    Printing drugs? A New Zealand politician suggested last year that it would soon be possible to 3D print gold, if he didn’t put a stop to it: http://www.stuff.co.nz/technology/gadgets/30017857/Printers-capable-of-making-guns

    (Not sure how you’d get the individual protons and neutrons to stay in place. Maybe using a Bose-Einstein condensate. Which aisle at Home Depot is that in?)

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