The number of active pharmaceutical ingredients (API) with sub-optimal physiochemical properties, such as poor solubility, dissolution and physical / chemical stability has increased over the last decade as generally APIs have become more complex. The solid form strongly influences these properties, and it is vitally important to understand and manufacture the appropriate solid form. Salts and co-crystals have been identified as viable solid forms that may improve the aforementioned properties of development candidates.
In this webinar hosted by Scientific Update, Veranova Solid Form Scientists, Shane Cullen and Jethro Beamish-Cook, explore the case of a small organic molecule and agrochemical active, pyrimethanil (a broad-spectrum fungicide) and 3-nitrobenzoic acid (counterion/ coformer), which can form either a kinetic salt or a thermodynamic cocrystal depending on the crystallization process.
Crystallization control is crucial for obtaining desired metastable forms. They discuss the discovery of these forms through comprehensive salt/cocrystal/polymorph screening and the subsequent investigation of solubility to guide crystallization development. By understanding solubility, Veranova has established robust routes to both the salt and cocrystal forms. Finally, they delved into the scale-up of these moieties using jacketed reactors and the implementation of particle engineering controls, including design of experiments, milling (jet and wet milling) to achieve desired crystallization outcomes.
