Paradigm Shifted Pharmaceutical Process Introduced by Spherical Crystallization

Abstract

In this chapter, we explain how paradigm shifted physicochemical properties suitable for direct tableting of APIs without using an excipient, such as a binder or disintegrant, can be provided by spherical crystallization. Simultaneous designing of primary and secondary particle properties is performed. Critical operating parameters determining the micromeritic properties of the materials are the temperature, combination ratio of solvents for crystallization, and agitation speed. The way how spherically agglomerated API crystals can improve pharmaceutical processing is explained based on their paradigm shifted mechanical properties. Agglomerated crystals placed under low environmental pressure, such as inside a hopper for tableting or capsule filling, flow evenly because they behave like coarse single particles. On the other hand, agglomerated crystals placed under a high pre-consolidated pressure, like when they are tableted, are disintegrated into the original particles (or even finer ones) with the creation of a new surface having a higher surface energy. They can reform to have a stronger internal structure due to the stronger binding force arising at the contact points of the particles in the tablet. The way how spherically agglomerated API crystals can be directly tableted without using a binder is explained based on the paradigm shifted compaction behavior of spherically crystallized products appearing under static and dynamic compactions. The slope of the straight line in Heckel’s plot at a later stage of compaction of the agglomerate is greater than that of the original crystals, suggesting that the crystals separated from the agglomerate are more plastically compressible than the original crystals. Due to reduced recovery of elastic stress with agglomerated crystals results in reducing ejection force, improving the tabletability of the agglomerated crystals by avoiding tablet hindrances, such as capping or others.