Investigating the Mechanism of l-Valine in Improving the Stability of Gabapentin Combining Chemical Analysis Experiments with Computational Pharmacy
Abstract
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.
KEY WORDS
Stability Computational pharmacy Hydrogen bond Reaction barriers Polymorphic drugs Amino acidNotes
Funding
This work was supported by Shanghai Science and Technology Commission R&D Platform Special (18DZ2290500).
Compliance with Ethical Standards
Disclaimers
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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