Abstract
Purpose. The aim of this study was to clarify the quantitativerelationship between solubility, initial dissolution rate and heat of solution ofracemic compound and its enantiomers.
Methods. Propranolol, propranolol HCl, tyrosine, and tryptophan wereused as typical chiral drugs. The heat of solution of chiral drug wasmeasured by an isothermal microcalorimeter and the heat of fusionwas measured by a DSC. The free energy difference for the dissolutionof drug was calculated from the solubility and initial dissolution ratedata.
Results. The free energy difference and enthalpy difference of thedissolution between the racemic compound and enantiomer ofpropranolol, propranolol hydrochloride, tyrosine, and tryptophan were obtainedby the solubility, initial dissolution rate and heat of solution data. Agood linearity was observed in the free energy difference and theenthalpy difference for the dissolution of them, except for propranololHCl data. By considering the dissociation in solution, the data ofpropranolol HCl followed the regression line.
Conclusions. The free energy difference of the dissolution was linearlydependent on the enthalpy difference for the racemic compound andits enantiomers. The results fit the theoretical equation. It could bepossible to estimate the solubility of chiral insoluble drug from thethermal data.
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Yonemochi, E., Yoshihashi, Y. & Terada, K. Quantitative Relationship Between Solubility, Initial Dissolution Rate and Heat of Solution of Chiral Drugs. Pharm Res 17, 90–93 (2000). https://doi.org/10.1023/A:1007578811049
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DOI: https://doi.org/10.1023/A:1007578811049