For the engineering of Mometasone Furoate Monohydrate (MFM) to a final Particle Size Distribution (PSD) within the inhalation range, microfluidization of the API suspension was performed, followed by isolation by spray drying. The microfluidization stage ended with a D50 ~ 2.1 μm; however, during spray drying, increasing values of particle size were observed over time on the final dried material fractions.
To study whether the observed PSD instability on the dried powder was caused by Ostwald Ripening (OR) phenomenon of the API in suspension, two suspensions of MFM were microfluidized to a different final PS and stored at different temperatures. The observed PSD growth followed a profile that can be ascribed to OR, being dependent on both temperature and initial PSD.
In order to overcome PSD growth in suspension, an innovative engineering approach was put in place: Dynamic Suspension Drying (DSD). According to DSD, the suspension, after being processed by microfluidization at elevated pressure (and the PSD has plateau at the target values), is isolated in the form of a dried powder while continuously recycling the suspension to the microfluidization unit at an optimized mild pressure. These mild conditions prevent any increase or any reduction in the PSD, since only particle growth by OR is being prevented.
DSD was successful in preventing OR without the need of stabilizing agents, offering a substantial advantage over other approaches, because it is a much simpler and effective process that will not impact the final product properties (e.g., stability, bioavailability, performance, composition) or manufacturability.