✍ Scribed by Ahmad Y. Sheikh; Agnes Pal; Shekhar Viswanath; John C. Tolle
No coin nor oath required. For personal study only.
A modification of wet agglomeration technique is developed and demonstrated by agglomerative crystallization process for a nonapeptide (ABT-510) to improve processing of needle like crystals. Our procedure involves exploiting partial miscibility of the crystallization solvent system for in situ generation of a wetting agent with suitable agglomerative properties. Experiences with ABT-510 show that a relatively small fraction of phase separation (1-5%) is needed to create enough wetting agent for effective agglomeration. Manipulations in the properties and quantity of the wetting agent easily achieved by modifying process trajectories in the solvent space lead to significant variations in agglomerative particle shapes. An optimal process trajectory is established by thorough evaluation of solid-liquid equilibria, liquid-liquid equilibria, properties of the wetting agent and agglomerative particle shape. Optimum antisolvent addition profile is also established and the process scaled up using suitable process analytical tools (PAT) to monitor for consistent performance. This optimally designed agglomerative crystallization process consistently lead to agglomeration of the particles just inside the biphasic solvent region. Extremely rapid crystal form conversion to the desired crystalline form is also observed in the vicinity of the biphasic solvent region, probably as a consequence of density fluctuations generated by the onset of solvent immiscibility.
📜 SIMILAR VOLUMES
## Abstract It is demonstrated that in a case where neither the proton nor the natural‐abundance ^13^C‐satellite spectra of a partially oriented molecule carry enough structural information, one can determine the entire molecular geometry by the combined use of several liquid crystals as solvents.