Droplet-Templated Antisolvent Spherical Crystallization of Hydrophilic and Hydrophobic Drugs with an in situ Formed Binder

This study presents a novel droplet-templated antisolvent spherical crystallization method applicable to both hydrophilic and hydrophobic drugs. In both cases, an alginate hydrogel binder forms in situ, concurrently with the crystallization process, effectively binding the drug crystals into monodisperse spheres. This study presents a detailed process description with mass transfer modeling, and with characterization of the obtained alginate/drug spheres in terms of morphology, composition, and drug loading. Although glycine and carbamazepine are used as model hydrophilic and hydrophobic drugs, this method is easily generalized to other drugs, and offers several benefits such as minimal thermal impact, fast crystallization rates, high drug-binder loading ratios, and high selectivity toward metastable polymorphs.