Particle Design of Drugs via Spherical Crystallization: A Review from Fundamental Aspects to Technology Development

In the pharmaceutical industry, the production process of most active pharmaceutical ingredients involves at least one crystallization step. Design of drug spheres via various spherical crystallization technologies can impart crystals with certain superior attributes including high flowability and compressibility as well as excellent mechanical properties. Some new spherical crystallization approaches and design principles have been proposed in recent years. This review aims to review the up-to-date design principles and preparation technologies of drug spheres, providing a guide for design, preparation, and performance evaluation of the drug spheres. Herein, we review the mechanisms and design principles of the spherical crystallization first, and subsequently various technologies reported in the literature are reviewed with the critical process parameters being analyzed. Lastly, the challenges facing the development of spherical crystallization for drugs are discussed.