title: A novel accelerated oxidative stability screening method for pharmaceutical solids.
abstract: Despite the fact that oxidation is the second most frequent degradation pathway for pharmaceuticals, means of evaluating the oxidative stability of pharmaceutical solids, especially effective stress testing, are still lacking. This paper describes a novel experimental method for peroxide-mediated oxidative stress testing on pharmaceutical solids. The method utilizes urea-hydrogen peroxide, a molecular complex that undergoes solid-state decomposition and releases hydrogen peroxide vapor at elevated temperatures (e.g., 30°C), as a source of peroxide. The experimental setting for this method is simple, convenient, and can be operated routinely in most laboratories. The fundamental parameter of the system, that is, hydrogen peroxide vapor pressure, was determined using a modified spectrophotometric method. The feasibility and utility of the proposed method in solid form selection have been demonstrated using various solid forms of ephedrine. No degradation was detected for ephedrine hydrochloride after exposure to the hydrogen peroxide vapor for 2 weeks, whereas both anhydrate and hemihydrate free base forms degraded rapidly under the test conditions. In addition, both the anhydrate and the hemihydrate free base degraded faster when exposed to hydrogen peroxide vapor at 30°C under dry condition than at 30°C/75% relative humidity (RH). A new degradation product was also observed under the drier condition. The proposed method provides more relevant screening conditions for solid dosage forms, and is useful in selecting optimal solid form(s), determining potential degradation products, and formulation screening during development.
authors.affiliation: NCE Formulation Sciences-LC, Abbott Laboratories, Abbott Park, Illinois 60064-6120.
authors.forename: Donghua Alan
authors.initials: DA
authors.lastname: Zhu
authors.affiliation: NCE Formulation Sciences-LC, Abbott Laboratories, Abbott Park, Illinois 60064-6120.
authors.forename: Geoff G Z
authors.initials: GGZ
authors.lastname: Zhang
authors.affiliation: NCE Formulation Sciences-LC, Abbott Laboratories, Abbott Park, Illinois 60064-6120.
authors.forename: Karen L S T
authors.initials: KLST
authors.lastname: George
authors.affiliation: Oral Drug Product, Manufacturing Sciences and Technology, Abbott Laboratories, North Chicago, Illinois 60064. Electronic address: Deliang.Zhou@abbott.com.
authors.forename: Deliang
authors.initials: D
authors.lastname: Zhou
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D004355:Drug Stability; D004809:Ephedrine / Q000737:chemistry; D004867:Equipment Design; D005240:Feasibility Studies; D006861:Hydrogen Peroxide / Q000737:chemistry*; D013058:Mass Spectrometry; D016877:Oxidants / Q000737:chemistry*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D033362:Powder Diffraction; D013997:Time Factors; D014508:Urea / Q000737:chemistry*; D014835:Volatilization; D014961:X-Ray Diffraction
chemical_list: D016877:Oxidants; D004364:Pharmaceutical Preparations; D014508:Urea; D006861:Hydrogen Peroxide; D004809:Ephedrine