A new approach to accelerated drug-excipient compatibility testing.
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.
Sims
Jonathan L
JL
GlaxoSmithKline R & D, New Frontiers Science Park, Harlow, Essex, UK. jon_sims-1@gsk.com
Carreira
Judith A
JA
Carrier
Daniel J
DJ
Crabtree
Simon R
SR
Easton
Lynne
L
Hancock
Stephen A
SA
Simcox
Carol E
CE
D002626:Chemistry, Pharmaceutical; D004344:Drug Incompatibility; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D015203:Reproducibility of Results; D013607:Tablets
D005079:Excipients; D004364:Pharmaceutical Preparations; D013607:Tablets