(427b) Enabling Desired Particle Morphology and Polymorphism In Crystal Agglomeration | AIChE

(427b) Enabling Desired Particle Morphology and Polymorphism In Crystal Agglomeration


Wang, C. - Presenter, Bristol-Myers Squibb Company
Chang, S. - Presenter, Bristol Myers Squibb

Various particle engineering techniques, such as temperature cycling, slurry milling, and solid micronization, are commonly employed in pharmaceutical process development and manufacturing to tailor desired crystal size, powder specific surface area, primary crystal morphology, and other associated powder characteristics.  Crystal agglomeration provides another avenue to improve various powder properties, especially for compounds that have a crystal morphology that is difficult to modify by classical crystallization techniques.  The primary crystals which frequently have a needle-like or rod-like morphology can be directed to form agglomerates in a multi-solvent system.  The resultant agglomeration drastically improves slurry filterability and bulk powder properties in comparison with those of the primary crystals.  

The development focus of a crystal agglomeration process for pharmaceutical intermediates and active pharmaceutical ingredients (APIs) can vary.  While the improvement of slurry filterability is a common goal for processing both intermediates and APIs, the target polymorph must also be achieved in the API process.  A systematic approach, including crystallization solvent selection,  polymorph screening, solvent-solid interaction characterization, and crystallization process optimization, is investigated to identify potential solvents and process parameters to promote crystal agglomeration and control desired particle size and crystal form.  This approach will be supported by case studies throughout the presentation.