The Impact of Crystal Habit on the Pharmaceutical Properties of Active Pharmaceutical Ingredients

Abstract

Crystal habit modification potentially improves the pharmaceutical and biopharmaceutical properties related to active pharmaceutical ingredients (APIs) and is an important aspect of crystal engineering. It has been demonstrated that filterability, compaction properties, flow behavior, and dissolution performance of APIs are dependent on the crystal habit of the compound, which ultimately depends upon the combination of factors including but not limited to the nature of solvent, additives, supersaturation, the environment provided during crystallization, etc. Crystal habit modification may be considered as an economically viable approach to mitigate pharmaceutical manufacturing challenges. This tutorial provides a step-by-step approach to crystal habit modification using different crystallization methods. Also, the factors that affect crystallization experiments at each stage of the different methods are explained in detail. The effects of supersaturation, solute-solvent interactions, additives, rate of crystallization, etc., are described, with examples. The impact of crystal habits on pharmaceutical properties such as filtration, punch sticking, compressibility, dissolution rate, etc., is also explained in detail with case studies. Finally, the analytical methods that are useful in the characterization of crystalline materials (morphological, physicochemical, rheological, and surface characterization) are explained, along with the experimental procedures involved.