title: 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.
authors.affiliation: Analytical Research and Development, Pfizer Global Research and Development, Groton, Connecticut, USA. wendy_cory@groton.pfizer.com
authors.forename: Wendy
authors.initials: W
authors.lastname: Cory
authors.forename: Kelly
authors.initials: K
authors.lastname: Field
authors.forename: Dan
authors.initials: D
authors.lastname: Wu-Linhares
mesh_terms: D000327:Adsorption / Q000187:drug effects; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D004344:Drug Incompatibility; D005079:Excipients / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008353:Mannitol / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry / Q000302:isolation & purification; D011208:Powders / Q000737:chemistry / Q000302:isolation & purification; D012997:Solvents / Q000737:chemistry; D013607:Tablets / Q000737:chemistry / Q000302:isolation & purification; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards*; D014867:Water / Q000737:chemistry
chemical_list: D005079:Excipients; D010880:Piperidines; D011208:Powders; D012997:Solvents; D013607:Tablets; D014867:Water; D008353:Mannitol; D002482:Cellulose; D002266:Carboxymethylcellulose Sodium; C109691:microcrystalline cellulose; D006851:Hydrochloric Acid; C099414:(2S,3S)-2-phenyl-3-((5-trifluoromethoxy-2-methoxy)benzylamino)piperidine