From Vials to Vessels: Discovery and Development of a Salt / Cocrystal Switch - Demonstrating Process Control at Scale incorporating Particle Engineering Strategies

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.

This talk explored 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. We discussed the discovery of these forms through comprehensive salt/cocrystal/polymorph screening and the subsequent investigation of solubility to guide crystallization development. By understanding solubility, we have established robust routes to both the salt and cocrystal forms. Finally, we will 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.

The presentation will be of interest to scientists/ chemists in small to medium biotechs and large pharma as well as in the agrochemical industry, specifically:

• R&D scientists
• Crystallization scientists
• Analytical scientist
• Head of discovery
• Head of Process Chemistry
• Head of Chemical Development
• Head of Crystallization
• Agro-Science Group
• Consultants

The webinar was presented by Dr Shane Cullen and Dr Jethro Beamish-Cook and is sponsored by Veranova