Thermodynamic and molecular investigation into the solubility, stability and self-assembly of gabapentin anhydrate and hydrate. (October 2017)

• Record Type: Journal Article
• Authors: Wang, Yan; Du, Shichao; Wu, Songgu; Li, Long; Zhang, Dejiang; Yu, Bo; Zhou, Lina; Bekele, Hibest kiflegiorgis; Gong, Junbo
• Is Part Of: Journal of chemical thermodynamics. Volume 113(2017)
• Page Start: 132
• Page End: 143
• Publication Date: 2017-10
• Subjects: Gabapentin -- Solubility -- Molecular dynamic simulation -- Water activity -- Stability; Thermodynamics -- Periodicals; Thermochemistry -- Periodicals; Thermodynamique -- Périodiques; Thermochimie -- Périodiques; Thermochemistry; Thermodynamics; Periodicals; 541.369
• DOI: 10.1016/j.jct.2017.05.041
• Languages: English
• ISSNs: 0021-9614

Abstract

Graphical abstract: In alcohol-water system, gabapentin anhydrate can transform to monohydrate with the increasing of water, which is influenced both by temperature and water activity. The solubility of anhydrate/hydrate have strange trend, especially existing a minimum in water rich region. Molecular dynamics simulations show the water association and solvent-solute interactions are the key factors. Highlights: Solubility of gabapentin anhydrate/monohydrate in alcohol-water mixtures was experimentally determined. Molecular dynamics simulations were carried out to explore the effect of solvent composition on the solubility. Critical water activity and the transition temperature of gabapentin anhydrate/hydrate were determined. Ternary phase diagram of (gabapentin-ethanol-water) at 293.15 K was built. Abstract: Solubility of gabapentin anhydrate/monohydrate in alcohol-water mixtures was experimentally determined. An interesting trend of the solubility was found, which showed both maximum and minimum solubility with different solvent compositions at one temperature. Molecular dynamics simulations were carried out to explore the effect of solvent composition on the solubility, indicating that the water association played an important role. Critical water activity and the transition temperature of gabapentin anhydrate/hydrate were also determined, and a relationship between them was established to investigate the factors influencing the hydration. Furthermore, the ternary phase diagram of (gabapentin-ethanol-water) at 293.15 K was built by slurry experiments for further understanding of the crystal form transformation, which confirmed the stability regions of anhydrate/monohydrate and verified the above established relations. Then the dehydration/hydration process in the solution can be predicted and controlled, thus obtaining the desired product.