The Interaction between Gabapentin and Cations to Improve Its Stability
YANG Li-xiang1, LI Dai-xi1*, LIU Bao-lin1, WEI Dong-qing2, GUO Bai-song3, LUAN Han-sen4, XI Quan4, WANG Hao4
1. Institute of Food Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China; 2. State Key Laboratory of Microbial Metabolism, Shanghai Jiaotong University, Shanghai 200240, China; 3. Injection Laboratory, Shanghai Tofflon Science and Technology Co., Ltd., Shanghai 201108, China; 4. China State Institute of Pharmaceutical Industry, Shanghai 201203, China
Abstract��OBJECTIVE To reduce the occurrence of subsidiary reaction by studying the effects of different ions on the dehydration condensation reaction mechanism and energy barrier of gabapentin. METHODS The molecular structure of the drug before and after adding different ions were optimized using the density functional theory (DFT) with B3LYP method at the 6-311+G (d, p) basis set level, and its structural parameters and thermodynamic parameters were calculated. RESULTS The energy barriers of the subsidiary reaction obviously increased no matter what cations were added, and zinc ion was the best. CONCLUSION It was proved that cations can effectively inhibit gabapentin from compensating to produce 3,3-pentamethylene-4-butyrolactam. The mechanism is using proper ion to change electrostatic interaction and the electron distribution of the active groups on the reactant so as to increase the barrier of the subsidiary reaction of gabapentin, thus inhibiting the occurrence of dehydration condensation reaction.
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YANG Li-xiang, LI Dai-xi, LIU Bao-lin, WEI Dong-qing, GUO Bai-song, LUAN Han-sen, XI Quan, WANG Hao. The Interaction between Gabapentin and Cations to Improve Its Stability. Chinese Pharmaceutical Journal, 2018, 53(19): 1658-1666.
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2018, Vol. 53 
