PMID- 30761435
OWN - NLM
STAT- MEDLINE
DCOM- 20190405
LR  - 20190405
IS  - 1530-9932 (Electronic)
IS  - 1530-9932 (Linking)
VI  - 20
IP  - 3
DP  - 2019 Feb 13
TI  - Investigating the Mechanism of L-Valine in Improving the Stability of Gabapentin 
      Combining Chemical Analysis Experiments with Computational Pharmacy.
PG  - 114
LID - 10.1208/s12249-019-1312-4 [doi]
AB  - The mechanism of L-Val on how to improve the stability of gabapentin (GBP) was 
      described by the combination of chemical analysis experiments and computer 
      simulations. Scanning electron microscope (SEM), powder X-ray diffraction (PXRD), 
      and differential scanning calorimeter (DSC), coupled with attenuated total 
      reflectance Fourier transform infrared spectroscopy (ATR-FTIR), were used to 
      identify beta-GBP prepared by rapid solvent removal method. The reaction barriers on 
      crystal planes, beta-GBP (100) and beta-GBP (10-1), are smaller than alpha-GBP and gamma-GBP, 
      reaching 276.65 kJ/mol and 299.57 kJ/mol, respectively. Thus, it was easier for 
      beta-GBP to form lactam, and the occurrence of beta-GBP would lead the worse stability 
      of alpha-GBP. The addition of neutral amino acids such as L-Val could improve the 
      stability of alpha-GBP effectively. The adsorption energy of alpha-GBP (002) crystal 
      plane with L-Val is larger than that of other crystal planes, reaching 
      42.17 kJ/mol. Hydrogen bond was the combination of L-Val and GBP main crystal 
      planes, which could inhibit the crystal transformation of alpha-GBP. These results 
      suggest that neutral amino acid protectants, such as L-Val, could improve the 
      stability of alpha-GBP effectively, and inhibition of crystal transformation is one 
      of the effective methods to improve the stability of polymorphic drugs.
FAU - Wang, Jiaxin
AU  - Wang J
AD  - National Pharmaceutical Engineering Research Center, China State Institute of 
      Pharmaceutical Industry, Shanghai, China. wangjiaxin0108@163.com.
FAU - Yang, Lixiang
AU  - Yang L
AD  - School of Medical Instrument and Food Engineering, University of Shanghai for 
      Science and Technology, Shanghai, China.
FAU - Li, Daixi
AU  - Li D
AD  - School of Medical Instrument and Food Engineering, University of Shanghai for 
      Science and Technology, Shanghai, China.
FAU - Xu, Ying
AU  - Xu Y
AD  - National Pharmaceutical Engineering Research Center, China State Institute of 
      Pharmaceutical Industry, Shanghai, China.
AD  - School of Pharmacy, Fudan University, Shanghai, China.
FAU - Yang, Li
AU  - Yang L
AD  - National Pharmaceutical Engineering Research Center, China State Institute of 
      Pharmaceutical Industry, Shanghai, China.
FAU - Zhao, Hong
AU  - Zhao H
AD  - National Pharmaceutical Engineering Research Center, China State Institute of 
      Pharmaceutical Industry, Shanghai, China.
FAU - Zhu, Zhuangzhi
AU  - Zhu Z
AD  - National Pharmaceutical Engineering Research Center, China State Institute of 
      Pharmaceutical Industry, Shanghai, China.
FAU - Luan, Hansen
AU  - Luan H
AD  - National Pharmaceutical Engineering Research Center, China State Institute of 
      Pharmaceutical Industry, Shanghai, China. luanhansen@sina.com.
FAU - Luo, Qiong
AU  - Luo Q
AD  - Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Shanghai, 
      China. simple_smileluo@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20190213
PL  - United States
TA  - AAPS PharmSciTech
JT  - AAPS PharmSciTech
JID - 100960111
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Solutions)
RN  - 0 (beta-Lactams)
RN  - 059QF0KO0R (Water)
RN  - 6CW7F3G59X (Gabapentin)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Calorimetry, Differential Scanning
MH  - *Computer Simulation
MH  - *Drug Stability
MH  - Excitatory Amino Acid Antagonists/*chemistry
MH  - Gabapentin/*chemistry
MH  - Hydrogen Bonding
MH  - Hydrogen-Ion Concentration
MH  - Microscopy, Electron, Scanning
MH  - Powder Diffraction
MH  - Solutions
MH  - Spectroscopy, Fourier Transform Infrared/methods
MH  - Valine/*chemistry
MH  - Water
MH  - beta-Lactams/chemical synthesis
OTO - NOTNLM
OT  - Amino acid
OT  - Computational pharmacy
OT  - Hydrogen bond
OT  - Polymorphic drugs
OT  - Reaction barriers
OT  - Stability
EDAT- 2019/02/15 06:00
MHDA- 2019/04/06 06:00
CRDT- 2019/02/15 06:00
PHST- 2018/09/19 00:00 [received]
PHST- 2019/01/14 00:00 [accepted]
PHST- 2019/02/15 06:00 [entrez]
PHST- 2019/02/15 06:00 [pubmed]
PHST- 2019/04/06 06:00 [medline]
AID - 10.1208/s12249-019-1312-4 [pii]
AID - 10.1208/s12249-019-1312-4 [doi]
PST - epublish
SO  - AAPS PharmSciTech. 2019 Feb 13;20(3):114. doi: 10.1208/s12249-019-1312-4.