Spray drying is a commonly used process for producing amorphous solid dispersions (ASDs) of drugs that are poorly water soluble.  This requires the use of large volumes of organic solvents to dissolve the drug and polymer prior to processing.  Drug molecules have become increasingly insoluble in organic solvents resulting in the use of more aggressive solvents.  Solvents such as dichloromethane can often solubilize the drug molecule, but the trade-off is a process with higher environmental and safety impacts from the solvent choice.  Given the large reliance on organic solvents, sustainability of the spray drying process must be considered for this technology to continue advancing critical medicines.  One approach that this talk will focus on is using volatile processing aids to increase drug solubility in preferred and more environmentally friendly solvents like methanol. This reduces the amount of solvent required to manufacture ASDs and uses solvents that do not have the negative environmental impacts. For weakly basic compounds, acetic acid in small quantities has been shown to increase solubility in methanol by ionizing the drug. A case study with gefitinib, a poorly soluble weakly basic compound, showed a 10-fold increase in solubility in a methanol:water blend with only 21.8 mg/mL acetic acid added compared to methanol:water without acetic acid. Acetic acid can be removed below ICH limits using typical tray drying conditions to regenerate the ingoing form of the drug. The large increase in solubility results in a significant increase in throughput for the spray drying process without using solvents that have negative environmental risks and also reduces the solvent consumption 12.3-fold. An analogous approach can be used for weakly acidic compounds using ammonia as a volatile basic processing aid. These processing aids can enable manufacture of ASDs of poorly soluble compounds to decrease manufacturing times, solvent quantities, costs and emissions.

Dramatic reduction of solvent usage in pharmaceutical spray drying using processing aids

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