Quantitative relationship between solubility, initial dissolution rate and heat of solution of chiral drugs.
OBJECTIVE
The aim of this study was to clarify the quantitative relationship between solubility, initial dissolution rate and heat of solution of racemic compound and its enantiomers.


METHODS
Propranolol, propranolol HCl, tyrosine, and tryptophan were used as typical chiral drugs. The heat of solution of chiral drug was measured by an isothermal microcalorimeter and the heat of fusion was measured by a DSC. The free energy difference for the dissolution of drug was calculated from the solubility and initial dissolution rate data.


RESULTS
The free energy difference and enthalpy difference of the dissolution between the racemic compound and enantiomer of propranolol, propranolol hydrochloride, tyrosine, and tryptophan were obtained by the solubility, initial dissolution rate and heat of solution data. A good linearity was observed in the free energy difference and the enthalpy difference for the dissolution of them, except for propranolol HCl data. By considering the dissociation in solution, the data of propranolol HCl followed the regression line.


CONCLUSIONS
The free energy difference of the dissolution was linearly dependent on the enthalpy difference for the racemic compound and its enantiomers. The results fit the theoretical equation. It could be possible to estimate the solubility of chiral insoluble drug from the thermal data.
Yonemochi
E
E
School of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, Japan.
Yoshihashi
Y
Y
Terada
K
K
D006358:Hot Temperature; D011433:Propranolol / Q000737:chemistry; D012995:Solubility; D012996:Solutions; D013237:Stereoisomerism; D013816:Thermodynamics
D012996:Solutions; D011433:Propranolol