AAPS PharmSciTech

, 20:114 | Cite as

Investigating the Mechanism of l-Valine in Improving the Stability of Gabapentin Combining Chemical Analysis Experiments with Computational Pharmacy

  • Jiaxin WangEmail author
  • Lixiang Yang
  • Daixi Li
  • Ying Xu
  • Li Yang
  • Hong Zhao
  • Zhuangzhi Zhu
  • Hansen LuanEmail author
  • Qiong LuoEmail author
Research Article


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 β-GBP prepared by rapid solvent removal method. The reaction barriers on crystal planes, β-GBP (100) and β-GBP (10-1), are smaller than α-GBP and γ-GBP, reaching 276.65 kJ/mol and 299.57 kJ/mol, respectively. Thus, it was easier for β-GBP to form lactam, and the occurrence of β-GBP would lead the worse stability of α-GBP. The addition of neutral amino acids such as l-Val could improve the stability of α-GBP effectively. The adsorption energy of α-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 α-GBP. These results suggest that neutral amino acid protectants, such as l-Val, could improve the stability of α-GBP effectively, and inhibition of crystal transformation is one of the effective methods to improve the stability of polymorphic drugs.


Stability Computational pharmacy Hydrogen bond Reaction barriers Polymorphic drugs Amino acid 



This work was supported by Shanghai Science and Technology Commission R&D Platform Special (18DZ2290500).

Compliance with Ethical Standards


The views expressed in the manuscript entitled “Investigating The Mechanism of L-Valine In Improving The Stability of Gabapentin Combining Chemical Analysis Experiments With Computational Pharmacy,” which we wish to be considered for publication in “AAPS PharmSciTech,” are my own and not an official position of the institution or funder.


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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  1. 1.National Pharmaceutical Engineering Research CenterChina State Institute of Pharmaceutical IndustryShanghaiChina
  2. 2.School of Medical Instrument and Food EngineeringUniversity of Shanghai for Science and TechnologyShanghaiChina
  3. 3.School of PharmacyFudan UniversityShanghaiChina
  4. 4.Department of Nuclear MedicineShanghai Tenth People’s HospitalShanghaiChina

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