Methanol-assisted Secondary Drying to Accelerate Residual Solvent Removal in Spray-dried Polymers

Drug candidates with low aqueous solubility require bioavailability enhancement techniques to enable oral delivery. Spray drying has been used to manufacture amorphous solid dispersions with enhanced oral bioavailability, resulting in over a dozen commercial products and many more in clinical trials. After spray drying is used to convert a liquid feed to a solid powder, residual solvent remains in the product, which must be removed to meet ICH safety specifications. The process of residual solvent removal is called secondary drying. Typical secondary drying techniques, such as drying in the presence of water vapor or vacuum drying often suffice. Some spray-dried materials are more challenging, requiring 24 hours or longer to secondary dry at typical conditions. This work introduces methanol-assisted secondary drying, a technique which can be used to accelerate residual solvent removal from spray-dried products.