title: A new approach to accelerated drug-excipient compatibility testing.
abstract: The purpose of this study was to develop a method of qualitatively predicting the most likely degradants in a formulation or probing specific drug-excipient interactions in a significantly shorter time frame than the typical 1 month storage testing. In the example studied, accelerated storage testing of a solid dosage form at 50 degrees C, the drug substance SB-243213-A degraded via the formation of two oxidative impurities. These impurities reached a level of 1% PAR after 3 months. Various stressing methods were examined to try to recreate this degradation and in doing so provide a practical and reliable method capable of predicting drug-excipient interactions. The technique developed was able to mimic the 1-month's accelerated degradation in just 1 hr. The method was suitable for automated analysis, capable of multisample stressing, and ideal for use in drug-excipient compatibility screening.
authors.affiliation: GlaxoSmithKline R & D, New Frontiers Science Park, Harlow, Essex, UK. jon_sims-1@gsk.com
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Sims
authors.forename: Judith A
authors.initials: JA
authors.lastname: Carreira
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Carrier
authors.forename: Simon R
authors.initials: SR
authors.lastname: Crabtree
authors.forename: Lynne
authors.initials: L
authors.lastname: Easton
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Hancock
authors.forename: Carol E
authors.initials: CE
authors.lastname: Simcox
mesh_terms: D002626:Chemistry, Pharmaceutical; D004344:Drug Incompatibility; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results; D013607:Tablets
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D013607:Tablets