Enhanced percutaneous absorption of ionizable water-soluble drugs.
The percutaneous absorption of diltiazem hydrochloride (DIL) and disodium cromoglycate (DSCG) [representative, respectively, of cationic and anionic water-soluble drugs] was studied in rabbits, using films prepared from water-soluble components. When corresponding fat-soluble counter-ions were added to films prepared using the electrically neutral components polyvinylalcohol and glycerol, the percutaneous absorption of the drugs was enhanced. Furthermore, when non-electrolytes such as BL-9EX or urea were added to the films together with the counter-ions, the bioavailability of the drugs increased. Consequently, it is postulated that ionizable water-soluble drugs are absorbed through skin by forming fat-soluble ion-pairs and additionally that the barrier function against absorption is reduced by non-electrolytes such as BL-9EX or urea. Such non-electrolytes must not hinder the formation of ion-pairs between the drugs and corresponding counter-ions.
Ishikura
T
T
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Nagai
T
T
Sakai
Y
Y
Shishikura
T
T
Ebisawa
H
H
Machida
Y
Y
D000818:Animals; D001682:Biological Availability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000493:pharmacokinetics; D004110:Diltiazem / Q000008:administration & dosage / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D008567:Membranes, Artificial; D011817:Rabbits; D012869:Skin Absorption; D012995:Solubility
D008567:Membranes, Artificial; D004110:Diltiazem; D004205:Cromolyn Sodium