Elusive Seed Formation via Electrical Confinement: Control of a Novel Cocrystal in Cooling Crystallization

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Pharmaceutical co-crystals are multicomponent materials formed to enhance the properties of active pharmaceutical ingredients (APIs); they are commercially used to increase the number of drug candidates that successfully make it through the drug discovery pipeline. Nevertheless, the industrial production of co-crystals and other elusive solid forms remains a challenge. The main limitations are due to challenges related to scale up, solid form control and undesirable parameters needed for the preparation method. This study leverages the features of electrospray crystallization to generate elusive co-crystal forms that contain the APIs acetaminophen (paracetamol) and its regioisomer metacetamol. We report the formation of a new co-crystal, held together by van der Waals interactions and the use of the newly electrosprayed co-crystals as seeds to tune the performance of cooling crystallization, allowing this commonly used crystallization method to produce the elusive co-crystal. The electrosprayed co-crystal displays a previously unseen sponge-like surface topology and a fourfold solubility enhancement over that of the single component APIs. This new technology expands the accessibility to new solid forms that were previously inaccessible by other crystallization methods.
Original languageEnglish
Pages (from-to)3310–3315
JournalCrystal Growth and Design
Issue number6
Early online date19 Apr 2021
Publication statusPublished - 2 Jun 2021


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