TY - JOUR
T1 - Feasibility of rapidly assessing reactive impurities mediated excipient incompatibility using a new method
T2 - A case study of famotidine-PEG system
AU - Saraf, Isha
AU - Modhave, Dattatray
AU - Kushwah, Varun
AU - Neshchadin, Dmytro
AU - Gescheidt, Georg
AU - Trausinger, Gert
AU - Melchior, Philipp
AU - Magnes, Christoph
AU - Paudel, Amrit
PY - 2020/1/30
Y1 - 2020/1/30
N2 - The present work demonstrates the utility of temperature controlled set up with pressurized headspace oxygen as an approach to effectively reduce the time required for solid-state drug-excipient compatibility study. To illustrate the utility, the incompatibility of polyethylene glycol (PEG) and polyethylene oxide (PEO) with Famotidine (Fam) was shown. Owing to thermal and oxidative stress, polyethylene ether moieties of PEG generated reactive impurities, resulting in the degradation of Fam. The chemical degradation was evaluated via liquid chromatography. Around 20% of degradation was observed in the pressurized oxygen set up, whereas, no degradation was found in the absence of oxidative stress. On increasing the excipient fraction, the Fam degradation increased proportionally. Formation of aldehydes and free radicals from excipients were proposed as the precursors for Fam degradation. The generation of aldehydes and free radicals was confirmed by infrared and Electron Spin Resonance (ESR) spectroscopic analysis, respectively. Overall, the present study demonstrated the utility of pressurized oxygen set up as a rapid and routine tool for studying drug-excipient incompatibility at temperatures relevant drug-product manufacture.
AB - The present work demonstrates the utility of temperature controlled set up with pressurized headspace oxygen as an approach to effectively reduce the time required for solid-state drug-excipient compatibility study. To illustrate the utility, the incompatibility of polyethylene glycol (PEG) and polyethylene oxide (PEO) with Famotidine (Fam) was shown. Owing to thermal and oxidative stress, polyethylene ether moieties of PEG generated reactive impurities, resulting in the degradation of Fam. The chemical degradation was evaluated via liquid chromatography. Around 20% of degradation was observed in the pressurized oxygen set up, whereas, no degradation was found in the absence of oxidative stress. On increasing the excipient fraction, the Fam degradation increased proportionally. Formation of aldehydes and free radicals from excipients were proposed as the precursors for Fam degradation. The generation of aldehydes and free radicals was confirmed by infrared and Electron Spin Resonance (ESR) spectroscopic analysis, respectively. Overall, the present study demonstrated the utility of pressurized oxygen set up as a rapid and routine tool for studying drug-excipient incompatibility at temperatures relevant drug-product manufacture.
KW - Drug degradation
KW - Excipient compatibility
KW - RapidOxy®
KW - Reactive impurities
KW - Stress method
UR - http://www.scopus.com/inward/record.url?scp=85072980143&partnerID=8YFLogxK
U2 - 10.1016/j.jpba.2019.112893
DO - 10.1016/j.jpba.2019.112893
M3 - Article
C2 - 31606565
AN - SCOPUS:85072980143
SN - 0731-7085
VL - 178
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
M1 - 112893
ER -