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 (gabapentinethanol- 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.

Compounds

#	Formula	Name
1	C9H17NO2	2-(1-(aminomethyl)cyclohexyl)acetic acid
2	C2H6O	ethanol
3	CH4O	methanol
4	C9H19NO3	2-(1-(aminomethyl)cyclohexyl)acetic acid monohydrate
5	H2O	water

Datasets

The table above is generated from the ThermoML associated json file (link above). POMD and RXND refer to PureOrMixture and Reaction Datasets. The compound numbers are included in properties, variables, and phases, if specificied; the numbers refer to the table of compounds on the left.
Type	Compound-#	Property	Variable	Constraint	Phase	Method	#Points
POMD	1	Mass density, kg/m3 ; Crystal	Temperature, K; Crystal Pressure, kPa; Crystal		Crystal	X-ray diffraction	1
POMD	4	Mass density, kg/m3 ; Crystal	Temperature, K; Crystal Pressure, kPa; Crystal		Crystal	X-ray diffraction	1
POMD	1 3 5	Mole fraction - 1 ; Liquid	Temperature, K; Liquid Solvent: Mole fraction - 5; Liquid	Pressure, kPa; Liquid	Liquid Crystal - 1	Gravimetric Method	79
POMD	1 3 5	Mole fraction - 1 ; Liquid	Temperature, K; Liquid Solvent: Mole fraction - 5; Liquid	Pressure, kPa; Liquid	Liquid Crystal of intercomponent compound 1	Gravimetric Method	21
POMD	1 2 5	Mole fraction - 1 ; Liquid	Temperature, K; Liquid Solvent: Mole fraction - 5; Liquid	Pressure, kPa; Liquid	Liquid Crystal - 1	Gravimetric Method	70
POMD	1 2 5	Mole fraction - 1 ; Liquid	Temperature, K; Liquid Solvent: Mole fraction - 5; Liquid	Pressure, kPa; Liquid	Liquid Crystal of intercomponent compound 1	Gravimetric Method	35
POMD	1 2 5	Mass fraction - 1 ; Liquid	Mass fraction - 5; Liquid	Temperature, K; Liquid Pressure, kPa; Liquid	Liquid Crystal - 1	Gravimetric Method	8
POMD	1 2 5	Mass fraction - 1 ; Liquid	Mass fraction - 5; Liquid	Temperature, K; Liquid Pressure, kPa; Liquid	Liquid Crystal of intercomponent compound 1	Gravimetric Method	6
POMD	1 3	Mole fraction - 1 ; Liquid	Temperature, K; Liquid	Pressure, kPa; Liquid	Liquid Crystal - 1	Gravimetric Method	9
POMD	1 5	Mole fraction - 1 ; Liquid	Temperature, K; Liquid	Pressure, kPa; Liquid	Liquid Crystal of intercomponent compound 1	Gravimetric Method	9
POMD	1 2	Mole fraction - 1 ; Liquid	Temperature, K; Liquid	Pressure, kPa; Liquid	Liquid Crystal - 1	Gravimetric Method	9

Thermodynamics Research Center / ThermoML | Journal of Chemical Thermodynamics

Thermodynamic and molecular investigation into the solubility, stability and self-assembly of gabapentin anhydrate and hydrate

Wang, Y.[Yan], Du, S.[Shichao], Wu, S.[Songgu], Li, L.[Long], Zhang, D.[Dejiang], Yu, B.[Bo], Zhou, L.[Lina], Bekele, H. k.[Hibest kiflegiorgis], Gong, J.[Junbo]

ABSTRACT