title: Rapid estimation of kinetic parameters for thermal decomposition of penicillins by modulated thermogravimetric analysis.
abstract: Modulated thermogravimetic analysis (MTGA) is evaluated for the rapid estimation of thermal stability using several penicillin antibiotics as model compounds. The MTGA technique utilizes an oscillatory temperature program to obtain Arrhenius kinetic parameters through a mass loss during thermal degradation. To evaluate the reliability of this technique, activation energies (E(a)), log pre-exponential factor (logZ), and log first order rate constants (logk) obtained by MTGA for the thermal decomposition of ampicillin anhydrous, ampicillin trihydrate, ampicillin sodium salt, and penicillin G potassium salt are compared to existing literature values. The logk values estimated by MTGA agreed well with literature values when the weight loss observed by MTGA was shown to be due to the first decomposition step of the compound. The E(a) and logZ values determined by MTGA did not consistently agree with literature values as these parameters increased with decreasing heating rate (beta). The increase in E(a) and logZ values with decreasing beta seemed to offset each other to some extent to yield a relatively consistent logk estimate regardless of beta.
authors.affiliation: Pharmaceutical Research and Development, World Wide Pharmaceutical Sciences, Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, MI 48105, USA. jonathan.miller@pfizer.com
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Miller
authors.forename: Uma J
authors.initials: UJ
authors.lastname: Kale
authors.forename: Siu-Man Kelvin
authors.initials: SM
authors.lastname: Lau
authors.forename: Landon
authors.initials: L
authors.lastname: Greene
authors.forename: Henry Y
authors.initials: HY
authors.lastname: Wang
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006358:Hot Temperature; D007700:Kinetics; D008956:Models, Chemical; D010406:Penicillins / Q000032:analysis*; D013997:Time Factors
chemical_list: D010406:Penicillins