Journal
JOURNAL OF PHARMACEUTICAL SCIENCES
Volume 101, Issue 6, Pages 2123-2133Publisher
ELSEVIER SCIENCE INC
DOI: 10.1002/jps.23115
Keywords
chemical stability; crystal defects; dehydration; milling; physical stability; solid-state stability; mathematical model
Funding
- FDA [HHSF223200819929C]
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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 degrees C60 degrees 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. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:21232133, 2012
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