Study of the textural changes occurring during a solid state polymorphic transformation induced by temperature and relative humidity

Following the synthesis steps, the isolation steps (filtration, drying, milling,...) applied on a drug substance (DS) may largely impact its textural properties (porosity, particles surface state, granulometry), hence its performances such as, for instance, flowability or compression behavior. We present here the changes of the texture of a DS agglomerates induced during the last steps of the manufacturing process (including grinding, densification, polymorphic conversion induced by temperature and relative humidity) as studied by mercury intrusion porosimetry (MIP). Initial and final samples have been also studied by gas adsorption (B.E.T. method), and scanning electron microscopy (SEM) techniques. SEM observation and interpretation of MIP curves demonstrate that the initial batch presents two types of open intra-granular pores (cone-shaped pores and pores between elementary particles). The change between the initial and final textural properties of the powdered samples was also followed by MIP analysis performed on intermediate samples. The sample obtained after the final stage of the process did not present conic pores, which have totally disappeared from the surface of the agglomerates probably because of the granulation induced during polymorphic conversion due to humidity and mechanical rotation of the reactor.