Dissolution and partitioning behavior of hydrophobic ion-paired compounds.
OBJECTIVE
This study was conducted to determine the effects of counterion hydrophobicity on organic/aqueous partition coefficients for hydrophobic ion paired (HIP) complexes. Furthermore, the coupled dissolution and reverse ion-exchange kinetics for dissolution of HIP complexes into aqueous electrolyte solutions were measured and mathematically modeled.


METHODS
HIP complexes of model drugs tacrine and l-phenylephrine were formed using linear sodium alkylsulfates and bis (2-ethylhexyl sodium sulfosuccinate). Equilibrium partition coefficients between chloroform and aqueous solutions for the complexes and the kinetics of dissolution of the complexes in buffered aqueous solutions were measured.


RESULTS
The chloroform/aqueous partition coefficients for l-phenylephrine/bis (2-ethylhexyl sodium sulfosuccinate) complexes decrease with increasing molar surface tension increment of salts added to the aqueous solution. The logarithm of the partition coefficient for a homologous series of alkyl sulfate complexes decreases as the hydrophilic-lipophilic balance number increases. Dissolution of HIP complexes in deionized water shows first order kinetics, whereas dissolution in aqueous electrolyte solutions shows biphasic kinetics. A kinetic model explains these dissolution rates.


CONCLUSIONS
Solubility and dissolution rates for HIP complexes depend on the hydrophobic-lipophilic balance number of the organic counter ion as well as on the electrolyte composition of aqueous solutions. Reverse ion-exchange kinetics are sufficiently slow to allow HIP complexes to be considered simple prodrugs.
Lengsfeld
C S
CS
University of Colorado at Boulder, Department of Chemical Engineering, Engineering Center, 80309, USA.
Pitera
D
D
Manning
M
M
Randolph
T W
TW
D057927:Hydrophobic and Hydrophilic Interactions; D007477:Ions / Q000737:chemistry*; D010656:Phenylephrine / Q000737:chemistry; D012995:Solubility; D013619:Tacrine / Q000737:chemistry
D007477:Ions; D010656:Phenylephrine; D013619:Tacrine