Transport of impurities and residual solvent during static drying

Siddique, Mariam and Laux, Audrey and Ottoboni, Sara and Price, Chris and Mulheran, Paul (2022) Transport of impurities and residual solvent during static drying. In: 13th World Filtration Congress, 2022-10-05 - 2022-10-09.

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The unwanted chemicals that remain within the API are termed impurities and may influence the stability and safety of pharmaceutical products.1 There are many impurities, including organic, inorganic, and residual solvents. Residual solvents are volatile organic chemicals used during manufacturing2 in addition to affecting the stability of the formulated product residual solvent can cause the formation of solid bridges leading to agglomeration. Any dissolved product or impurities in the solvent remaining in the filter cake following washing may be re-precipitated and retained in the cake and deposited during drying, reducing the product's purity.3 Therefore, it is essential to understand the impurity transport during isolation (washing and drying) to maintain product purity. The main objective of this work was to evaluate the relative transport of API, paracetamol (PCM) and impurities (blue dye, patent blue V) along with residual solvent (water or methanol) during static drying. For this, a solution of known concentration of PCM to which blue dye was added as an impurity that’s serve to track the transport of residual moisture through the cake. The solution with PCM and dye mimics the residual solvent, enabling quantification of the amount of residual solvent that can cause lump formation during drying. The concentration of PCM and blue dye was analysed by HPLC and UV-Vis analysis. It was demonstrated that different solutes and solvents show different transport behaviours depending on wettability and volatility. In the case of methanol as the solvent, the highest concentration of PCM and the blue dye remains within the lump formed at the point where the blue dye was added to the powder bed, but for water, the PCM remains concentrated in the lump which forms, however, the blue dye tends to migrate away from the lump. Experiments were performed using solvent mixture compositions and different solutes to further investigate the difference in behaviour between water and methanol. The Washburn method was used to evaluate wettability and contact angle with the different solute systems.