Effect of Variability of Physical Properties of Povidone K30 on Crystallization and Drug-Polymer Miscibility of Celecoxib-Povidone K30 Amorphous Solid Dispersions.

In the present study, we have investigated the variability in physical properties of povidone K30 (PVP K30) and its impact on crystallization and drug-polymer miscibility of celecoxib-PVP K30 (CLB-PVP K30) amorphous solid dispersions (ASDs). CLB-PVP K30 ASDs were prepared using nine batches of PVP K30, in situ on glass slides by quench-cooling using the hot and cold stage of a microscope. Crystallization of the ASDs stored at 40 ± 2 °C/75 ± 5% relative humidity was captured using polarized light microscopy for up to 24 h and quantified using mean pixel counts of images. The quantitative drug-polymer miscibility of nine CLB-PVP K30 systems was determined using melting point depression. Pearson's correlation analysis was used to find the correlation between (i) % crystallization with drug-polymer miscibility and physical properties and (ii) drug-polymer miscibility and physical properties, of PVP K30. The % crystallization was significantly variable (p < 0.05) among the nine CLB-PVP K30 ASDs. The nine PVP K30 batches exhibited significant variability (p < 0.05) from batch to batch and/or source to source in physical properties. The % crystallization showed correlation to particle size distribution (PSD) (weak positive), glass transition (Tg) (weak positive), drug-polymer miscibility (moderate negative), true density, and porosity (moderate positive) and hygroscopicity (strong positive). Miscibility showed correlation between Tg (weak positive), hygroscopicity (weak negative), PSD (moderate negative), and true density and porosity (strong negative). The study suggests PSD, hygroscopicity, true density, and porosity of PVP K30 as the functionality related characteristics for its intended functionality of physical stability when it is used as a stabilizer in ASDs.