[Trial for transdermal administration of sulfonylureas].
Sulfonylureas are widely used as oral hypoglycemic drugs in the treatment of non insulin dependent diabetes mellitus (NIDDM). Since sulfonylureas are usually taken for a long period, the compliance of the patients is very important. Therefore, for the improvement of the compliance of the patients, the development of a transdermal dosage form of sulfonylureas was attempted in this study. Glibenclamide (GLI) or chlorpropamide (CHL) was chosen as a principal agent and ointments were prepared by mixing 5% of GLI or CHL with a FAPG ointment base. Penetration and shearing stresses of the ointments were determined as physical characteristics of the ointments. There was no obvious difference of characteristics between the GLI ointment, or the CHL ointment and the FAPG ointment base. In drug release tests, the CHL ointment showed better release of the drug than the GLI ointment. In both ointments, comparatively rapid release of drug was observed in the initial 1 h, and continuous slow release was observed thereafter. When the ointments were applied on the back of male Wistar rats and the plasma glucose level was measured, both CHL and GLI ointments gave lower blood glucose levels than the control (FAPG base). At the all measuring points, the GLI ointment brought about significantly lower blood glucose levels than the control (p < 0.01). Thus, it was demonstrated that sulfonylureas were absorbed through the skin and lowered the blood glucose levels. The results suggest the possibility of transdermal administration of sulfonylureas for the treatment of NIDDM.
Takahashi
Y
Y
Department of Pharmacy, Yokohama City University Hospital, Kanagawa, Japan.
Furuya
K
K
Iwata
M
M
Onishi
H
H
Machida
Y
Y
Shirotake
S
S
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002747:Chlorpropamide / Q000493:pharmacokinetics*; D005905:Glyburide / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D008297:Male; D009824:Ointments; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009824:Ointments; D005905:Glyburide; D002747:Chlorpropamide