Formulation & polymorph screening

The problem

Characterization of Active Pharmaceutical Ingredients (APIs) goes beyond knowing the chemical structure. APIs can crystallize into different forms (polymorphs), each of which have their own solubility, bioavailability, and hydration stability. From an intellectual property standpoint, it’s also critical for researchers to identify all polymorphs for their API — before someone else does. All this means that it’s not enough to discover a new API. It’s also important to characterize it fully, by figuring out what conditions make it crystallize, and in which forms. This requires extensive polymorph screening by exploring a lot of conditions to generate crystals, including not just solvents but understanding how the presence of salts or potential co-crystals impact the crystal polymorph. Polymorph screening is a ton of work that usually requires a small army to get it all done.

The right tool for the job

Big Kahuna and Junior are automation platforms that can be configured to prepare crystallization plates, filter hot reagents, and integrate analytical results. The platforms bring together several key components needed to set up and run formulation and polymorph screening studies in small scale, letting you explore more formulations and polymorphs for your APIs than ever before.

What’s possible

Powder dispense

Solids can be dispensed from two formats. Large hoppers are best for one-to-many dispenses where the same powder goes into many destination wells. Hoppers are available in 10, 25, 50, and 100 mL volumes, and multiple hoppers of any combination can be set up on a Big Kahuna or Junior deck. If your typical polymorph screen requires you to dispense many different powders, switch to the Storage Vial (SV) hoppers. They work with standard 4 mL glass vials that are outfitted with a disposable dispense head. You can fit dozens of vials on deck, and hundreds off deck. These small hoppers allow for greater flexibility in solid dispensing.

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Heated liquid dispense

Big Kahuna and Junior have numerous options for dispensing liquids, the most useful being the heated, spreadable six tip. The temperature of the tip can go to 120 °C, and the pitch of the needles can vary from 9 – 20 mm, ensuring you get solutions in and out of a 96-well plate as well as a larger format vial. There is also an extendable tip if you just need one solution at a time, and the head can be put into 4-tip mode if that’s a better format for you.

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Heated filter block

Crystallization is very sensitive to the presence of a nucleator to initiate the crystal formation. Nucleators can lead to very irreproducible results. Automating the removal of these solid or small subvisible nucleator particles is accomplished by dispensing through a filter block that can be added to a Big Kahuna or Junior deck. This sandwich of filters and gaskets is heated up to 120 °C. This seals everything in and prevents evaporation and precipitation when you’re running polymorph screening experiments on this small of scale.

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Crystallizer block

The last critical step is crystallization. Big Kahuna and Junior can be set up with the heated six-tip liquid handler and a crystallization block. The block consists of plastic tubes sealed against a glass substrate. Crystals fall out of solution and settle on the glass substrate. The block can be heated or cooled so you can do multiple setups and compare crystallization conditions of the same reagents at different temperatures. When the experiment is done, disassemble the block and take that glass substrate over to an XRD or Raman to determine the structures.

Crystallizer block


Junior automates all your back-and-forth, over and over again, hands-on work. Explore more reaction and formulation conditions, prep samples, or hand off any other tasks you think would be better performed if you’re not the one doing it.

Big Kahuna

Big Kahuna gives you automated, high-throughput, end-to-end solutions for biologics, gene therapy vectors, small molecules, polymers and catalysts. It’s completely configurable and helps you save money and time while getting more work done.


Want more info?

Every lab has different bottlenecks and challenges. We’re all about partnering with you to build the bespoke solution that lets you do science faster and better. Have questions or can’t wait to speak with our expert team to find out what might be possible?