Role of solvent in differential phase behavior of celecoxib during spray drying

Spray drying is an industrially viable technique that can be used for modulation of the physical form of Active Pharmaceutical Ingredients (API), which is governed by inherent crystallization tendency and processing parameters during spray drying. In the current study, we investigated the role of solvent in differential phase behavior of celecoxib, a poor crystallizer, during spray drying and unveiled the underlying mechanisms. 1% w/v solutions of celecoxib in three different compositions of methanol (M)-water (W) solvent system were spray dried using a laboratory spray dryer. The proportions were 0, 5 and 10% v/v of water in methanol (MW0, MW5, and MW10, respectively). Percentage crystallinity of the spray dried products were evaluated using modulated differential scanning calorimetry and was in the order MW10 > MW5 > MW0 (i.e. 18.52% > 8.13% > 0%). Solution-state and solid-state crystallization events responsible for the experimental observations were probed using microscopy, Raman spectroscopy, and non-isothermal crystallization studies. An intermediate amorphous phase was generated for the studied samples, which underwent crystallization under the influence of chamber temperature for MW5 and MW10. Additionally, liquid-liquid phase separation (LLPS) at very high level of supersaturation led to relatively higher crystallinity for MW10. Insights from this work provide the basis for understanding of probable phase behavior of poor crystallizers during spray drying.