Intestinal absorption of drugs II. The effect of inclusion in cyclodextrins on the absorption of dantrolene

The inclusion of dantrolene sodium, a muscle relaxant with poor water-solubility, in-,- and-cyclodextrins was determined. Subsequently, the influence of the cyclodextrins on the absorption of the drug from aqueous solutions was investigated in a chronically isolated internal loop in the small intestine of the rat.A good correlation was found between the inclusion of dantrolene in the various cyclodextrins and the decrease in the absorption rate resulting from a reduction of the thermodynamically active dantrolene according to the phase-separation model. It was concluded that the cyclodextrins do not have a significant influence on the passage of dantrolene across the absorption barrier. Furthermore, experimental evidence was collected to support the fact that-cyclodextrin was absorbed to a limited, if not negligible, extent in the small intestine of the rat.     

Theoretical study on the sound absorption of electrolytic solutions. I. Theoretical formulation

A theory is formulated that describes the sound absorption of electrolytic solutions due to the relative motion of ions, including the formation of ion pairs. The theory is based on the Kubo-Green formula for the bulk viscosity. The time correlation function of the pressure is projected onto the bilinear product of the density modes of ions. The time development of the product of density modes is described by the diffusive limit of the generalized Langevin equation, and approximate expressions for the three- and four-body correlation functions required are given with the hypernetted-chain integral equation theory. Calculations on the aqueous solutions of model electrolytes are performed. It is demonstrated that the theory describes both the activated barrier crossing between contact and solvent-separated ion pairs and the Coulombic correlation between ions.     

Theoretical study on the sound absorption of electrolytic solutions. II. Assignments of relaxations

The theory on the ultrasonic absorption spectrum of electrolytic solutions recently proposed by us is applied to the model system that resembles to the aqueous solution of MgSO4. The charges on ions are reduced to +/-1.5e in order to obtain the equilibrium structure by the integral equation theory. The theory reproduces the existence of two relaxations around 100 kHz and 1 GHz. The physical origin of the relaxation is analyzed based on the theoretical expression. The slower relaxation is shown to originate in the formation of contact ion pair, in harmony with the conventional assignment. The amplitude of this relaxation agrees with the experimental one fairly well. The absorption cross section is a weakly increasing function of the concentration of the salt in theory, whereas it depends little on the concentration in experiment, which is ascribed to the weaker association of the pair in the theory. The deviation from the Debye relaxation is found for the faster process, and the concentration dependence is small. The analysis shows that this relaxation stems from the coupling between the pressure and the long-range concentration fluctuation, and the concentration independence and the non-Debye relaxation are explained based on the theoretical analysis. In particular, the theory demonstrates that this process has the t(-3/2) tail in the time domain, which is confirmed by numerical calculation. The deviation of the theoretical relaxation amplitude from the experimental one is elucidated in terms of the theoretical expression of the coefficient.