[Enhancing effect of switching iontophoresis on transdermal absorption of glibenclamide].
Glibenclamide(GLI) is widely used as an oral hypoglycemic drug in the treatment of non-insulin dependent diabetes mellitus (NIDDM). We investigated The enhancing effect of switching iontophoresis on the transdermal absorption and reduction of skin irritation to develop a transdermal dosage form of GLI. The 0.1% of Gli suspensions in 0.2 M tris-HCl buffer of pH 7.4, 8.0 and 8.5 were prepared as donor solutions. We examined drug permeation through the excised rat abdominal skin, drug absorption in rats and reduction of skin irritation after application of switching iontophoresis for 1 h using DC 10 V. The solubility of GLI in 0.2 M tris-HCl buffer increased with a rise in pH. In the permeation study, GLI was permeated continuously and the cumulative amount of permeated GLI increased using an alkaline donor solution. In the drug absorption study, the application group of pH 8.5 gave higher plasma concentration levels than those of pH 7.4 and 8.0 groups. The skin irritation evoked by the application of iontophoresis was pathologically studied. A total irritation score (TIS) was estimated as a judging standard for the skin damage. The TIS value increased dependently with a rise in pH. However, it was considered that the skin irritations were not serious and small matters. The results demonstrate the possibility of iontophoretic transdermal administration of GLI and the effect of drug solubility in the donor solution on the absorption of GLI.
Takahashi
Y
Y
Department of Pharmacy, Yokohama City University Medical Center, 4-57, Urafune-cho, Minami-ku, Yokohama 232-0024, Japan.
Iwata
M
M
Machida
Y
Y
D000818:Animals; D005905:Glyburide / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000009:adverse effects / Q000379:methods*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D012869:Skin Absorption; D023422:Skin Irritancy Tests; D012995:Solubility
D007004:Hypoglycemic Agents; D005905:Glyburide