Crystal Habit Modification to Improve Powder Flowability, a Case Study

In this investigation, experimental studies and possible mechanisms leading to the crystal habit modification of a developmental drug will be discussed. Crystallization was performed in various ways including anti-solvent addition and cooling crystallization. However, in all cases, the drug particles crystallized as long needles that resulted in poor powder flowability which was not suitable for formulation. Crystal engineering efforts were undertaken to improve the powder flowability by decreasing the aspect ratio of the primary drug particles. From the crystal habit modification techniques attempted, it was found that a combination of temperature cycling, “in situ seed generation” and wet milling was the technique that provided the largest decrease in the aspect ratio of primary drug particles. This resulted in a significant improvement of the powder flowability which enabled the formulation of the drug product.