Abstract

The study aims to elucidate the transformations of anhydrous olanzapine Form I (OLZ FI) into the hydrate forms, when stored at a high relative humidity or suspended in an aqueous media, in the presence of polymers. OLZ FI and physical mixtures (3:1 and 1:1, as powders or compacts) of olanzapine with polyethylene glycol (PEG-6000), polyvinylpyrrolidone (PVP K25) and hydroxypropylcellulose (HPC-LF) were stored (75%RH/25 °C, 75%RH/40 °C and 93%RH/25 °C) for 28 days. OLZ FI and the physical mixtures were also suspended in water under stirring (200 rpm/60 min). Samples were collected at different time points and vacuum filtered. OLZ FI showed to hydrate at 75%RH/25 °C when stored in the presence of HPC and PEG. At 93%RH all polymers affected the kinetics of hydration of OLZ FI with PVP as the only polymer with the ability to minimize the formation of the hydrate. When olanzapine was suspended in water with HPC and PVP the formation of the hydrate was inhibited. Compaction of the powders before storage led to an increase of the hydrate conversion rate of olanzapine on the first week of storage, due to a partial amorphisation of olanzapine present at the tablet surface. When stored at high humidity environments OLZ FI converted into dihydrate D and, when exposed to aqueous environments in the presence of different polymers converted into dihydrates B and E. From an industrial point of view, this study highlighted the importance of the excipient’s choice for OLZ formulations, so that a final OLZ medicine can have a consistent quality and performance throughout the entire medicine’s shelf life.

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