Is it the Method or the Process—Separating the Causes of Low Recovery

Abstract

During the development of a tablet formulation, a solvent capable of extracting 100% of the drug from the tablet excipients must be identified as part of the analytical assay method. When a low drug recovery from a tablet is observed with the assay method, it must be determined whether a problem with the manufacturing process exists, or if the extraction of the drug was incomplete. A solvent screen study was conducted with CP‐122,721 prototype formulations to select a robust solvent for the assay method. However, low tablet assay values (ca. 95%) were routinely observed during tablet formulation development and process scale up. Drug‐excipient interactions in a variety of solvents were subsequently evaluated to confirm the selection of the extraction solvent as capable of 100% extraction. At this point the focus of the investigation was placed on process‐related sources of low recovery, such as loss of drug to manufacturing equipment and/or segregation during the tableting process. The results suggest that the low drug recovery observed for the CP‐122,721 tablets was due to segregation during the manufacture, while the selected extraction solvent was able to eliminate any interactions between CP‐122,721 and the tablet excipients.