Particulate-Design Platform Developed by the Advanced Spherical Crystallization System

Abstract

In this chapter, we discuss how the spherical crystallization technique has been developed as a novel particulate-design platform to create various functional particulate preparations. The spherical crystallization technique is extensively advanced as a robust technology by modifying the process and formulation used for crystallization. If an API is poorly soluble in solvent, its acidic or alkaline solution is chosen as a good solvent. Spherical crystallization of a poorly soluble drug (Enoxacin) can be accomplished by developing a new ammonia diffusion system. This process is further advanced to prepare taste-masking microcapsules produced continuously with an acrylic polymer. Spherical crystallization was originally carried out using a tri-solvent system, that is, a good solvent, a poor solvent, and a bridging liquid, in which the crystallized particles were spherically agglomerated with a bridging liquid simultaneously induced from the system. It was recently found that if a good solvent solution is partially miscible in a poor solvent, the residual undissolved good solvent acts as a bridging liquid for the crystals, which can make the original spherical crystallization technique widely applicable to any other API with a binary-solvent system. Ascorbic acid crystals, as poorly compressible model crystals, are spherically agglomerated with a binary-solvent system, which enables direct tableting without requiring a binder. The improved tabletability of spherically agglomerated crystals of an originally poorly compressible powder is explained in terms of the strong plastic-deformation properties and very low elastic recovery of a compact of spherically agglomerated crystals during direct compression. To improve the physicochemical properties of APIs, including their solubility or therapeutic performance, a multi-component system was developed by adding a surfactant or hydrophilic polymer to the dispersing (poor) solvent. The solubility of the formulated drug can be enhanced by compounding a conformer that specifically interacts with the API. The solubility of indomethacin is enhanced by combining it with epirizole to form a new, spherically crystallized complex. Spherical crystallization with a double-API-component system, such as theophylline and ethylene diamine, can produce polymorphic aminophylline depending on the water content in the system. Polymeric spherical crystallization was developed for preparing polymeric drug carriers (microspheres, microballoons, PLGA nanospheres, etc.) for novel DDSs, which are explained in detail in Chaps. 5 and 6. Interestingly, the spherical crystallization process can be widely applied to semisolid materials like vitamin E, which are transformed into solid powders that can be filled in capsules or tableted with colloidal silica.