• Journal of Pharmaceutical Investigation
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• v.23 no.3
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• pp.41-50
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• 1993

The iontophoretic delivery across rat skin of quaternary ammonium salts (isopropamide: ISP, pyridostigmine: PS), which are positively charged over a wide pH range, was measured ill vitro. The study showed that: (a) iontophoresis significantly enhanced delivery of ISP and PS compared to respective passive transport; (b) delivery of ISP and PS was directly proportional to the applied continuous direct current density over the range of $0-0.69\;mA/cm^2;$ (c) delivery of ISP and PS was also proportional to the drug concentration in the donor compartment over the range of $0-2{\time}l0^{-2}M:$ (d) sodium ion in the donor compartment inhibited the drug transport possibly due to decreasing the electric transference number of the drug; (e) delivery of ISP and PS increased as the pH of the donor solution increased over the pH range 2-7 suggesting permselective nature of the epidermis, and inhibition of the transference number of the drugs by hydronium ion; (f) some organic anions such as taurodeoxycholate, salicylate and benzoate which form lipophilic ion-pair complexes with ISP inhibited the delivery of ISP. The degree of inhibition by the organic anions was linearly proportional to the extraction coefficient $(K_e)$ of ISP from the partition system with each counteranion between phosphate buffer (pH 7.4) and n-octanol. For PS, however, taurodeoxycholate, but not salicylate and benzoate inhibited the iontophoretic delivery. It suggests that not only sodium ion and hydronium ion but also the counteranions which form lipophilic ion-pairs with quaternary ammonium drugs are not favorable components in formulating the donor solution of the drugs to achieve an effective iontophoretic delivery.

• YAKHAK HOEJI
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• v.27 no.2
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• pp.125-131
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• 1983

Whether ($AB_{w}$) may be neglected against ($A_{w}^{+}$) in the calculation of the extraction coefficient of ion-pairs was criticized by both experiments and theoretical consideration, where ($AB_{w}$) and ($A_{w}^{+}$) mean the molar concentration of ion-pair AB and cation $A^{+}$ in the aqueous phase. Ion-pair complexes were partitioned between phosphate buffer (pH 7.4) and n-octanol. Tetrabutylammonium, isopropamide and methylene blue were selected as cations and benzoic acid, p-toluenesulfonic acid, salicylic acid and taurodeoxycholic acid were selected as counter ions (anions). As a result, conventional methods which assume no existence of ($AB_{w}$) were proven to lack generality. The equation proposed in my earlier report was confirmed to be valid as a general method.