title: Kinetic model for solid-state degradation of gabapentin.
abstract: Gabapentin degrades directly to gabapentin-lactam (gaba-L) in the solid state. The objective of this study was to formulate a drug degradation model that accounted for the environmental storage conditions and mechanical stress (prior to storage) on lactamization kinetics. The effects of mechanical stress on drug degradation kinetics were determined by milling gabapentin in a FRITSCH Planetary Micro Mill for 0 and 60 min. The resultant gabapentin powder was stored at 40 °C-60 °C and 5%-30% relative humidity. The rate of gaba-L formation was measured by high-performance liquid chromatography. An irreversible two-step autocatalytic reaction scheme was fit using nonlinear regression methods. The resultant kinetic model was used to predict the time-dependent concentration of degradant of gabapentin tablets prepared under various exemplary manufacturing conditions, thereby demonstrating the ability of the model to link manufacturing variation and chemical stability in solid-state gabapentin formulations.
authors.affiliation: College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Zong
authors.forename: Jiang
authors.initials: J
authors.lastname: Qiu
authors.forename: Radaduen
authors.initials: R
authors.lastname: Tinmanee
authors.forename: Lee E
authors.initials: LE
authors.lastname: Kirsch
mesh_terms: D000588:Amines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry*; D000077206:Gabapentin; D006868:Hydrolysis; D007700:Kinetics; D008962:Models, Theoretical; D033362:Powder Diffraction; D005680:gamma-Aminobutyric Acid / Q000737:chemistry*
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin