Effect of ointment bases on topical and transdermal delivery of salicylic acid in rats: evaluation by skin microdialysis.
Microdialysis has been used to determine the concentration of salicylic acid in skin tissue and plasma periodically for 4 h to evaluate the effect of ointment bases on topical and transdermal delivery of salicylic acid. The ointment bases examined were solbase (water-soluble), poloid and white petrolatum (oleaginous), hydrophilic poloid (water in oil (w/o) type emulsion lacking water) and absorptive ointment (w/o-type emulsion containing water). The ointments (0.1 g) containing 25 micromol salicylic acid were applied for 2 h to the surface of rat skin (1 cm2) with (intact) or without the stratum corneum. For intact skin, the extent of topical delivery from different ointments, evaluated by the area under the concentration-time curve (AUC) of salicylic acid in the skin tissue (AUCskin), increased in the order solbase << white petrolatum, poloid, hydrophilic poloid << absorptive ointment. The ratio of AUCskin (topical delivery) to the AUC of salicylic acid in plasma (AUCplasma, transdermal delivery) varied remarkably among the different bases, the greatest ratio being observed for absorptive ointment. When the ointments were applied to skin surface without stratum corneum, AUCskin for solbase was much higher (about 45 times that for intact skin), whereas only a small (two-fold) increase was observed for poloid and hydrophilic poloid and the increase was negligible for white petrolatum and absorptive ointment. For skin without the stratum corneum, the ratio AUCskin/AUCplasma for the different ointments was comparable, although the magnitudes of AUCskin and AUCplasma still varied substantially. The variance of AUC values arises as a result of the different rates of release of salicylic acid from the bases. These results indicate that: the topical and transdermal delivery of salicylic acid in intact skin varies substantially among different ointment bases, and the greatest topical delivery is observed for absorptive ointment; use of absorptive ointment increases the retention of salicylic acid in the stratum corneum; and the stratum corneum functions strongly as a penetration barrier for solbase, moderately for poloid and hydrophilic poloid, and less for absorptive ointment and white petrolatum.
Murakami
T
T
Department of Biopharmaceutics, Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Yoshioka
M
M
Okamoto
I
I
Yumoto
R
R
Higashi
Y
Y
Okahara
K
K
Yata
N
N
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000378:metabolism*; D004337:Drug Carriers; D066298:In Vitro Techniques; D008297:Male; D017551:Microdialysis; D009824:Ointments; D010232:Paraffin; D010577:Petrolatum; D011092:Polyethylene Glycols; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000008:administration & dosage / Q000378:metabolism*; D020156:Salicylic Acid; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D009824:Ointments; D012459:Salicylates; D011092:Polyethylene Glycols; D010232:Paraffin; D010577:Petrolatum; D020156:Salicylic Acid