Elaboration of a spherical agglomeration process: Case study of SAFINAMIDE MESYLATE
Résumé
bioavailability of the APIs has been drastically decreased (in 2013, 70 % of the drugs orally delivered under clinical development exhibited a low solubility in aqueous media [1]). The bioavailability of an API depends not only on its chemical nature but also on the physical properties of the particles; For instance, reducing the granulometry of the particles leads to an increase of the dissolution rate because of the increase of the specific surface area. However, decrease the granulometry of the particles impact the flowability properties of the powder and then the downstream processes (e.g. filtration, tableting processes, …) when manufacturing the drugs.
Spherical Agglomeration (SA) has been developed to overcome these issues. SA was first described by Kawashima et al. during the late 70’s [2]. It is part of the spherical crystallization methods and consists in the agglomeration of fine particles in suspension into spherical agglomerates using a bridging liquid. SA is governed by various parameters: stirring rate, addition method of the BL and amount of bridging liquid, agglomeration temperature and residence time. Each of them needs to be optimized to obtain the greater flowability properties.