sorbitan-monooleate and 2-mercaptoacetate

The in vivo percutaneous absorption and in vitro penetration of indomethacin (IND) and the calcium salt (IND-Ca) in ointments were investigated on rat abdominal skin under occlusions in the presence or absence of penetration enhancers. The absorption of IND-Ca from the gel (Hiviswako) ointment was significantly higher than that from a standard ointment of IND, an approximation of a commercial product. Sorbitan monooleate had no enhancer effect for the IND-Ca gel ointment, while the addition of calcium thioglycolate dramatically decreased the absorption of IND-Ca due to powdering of the ointment. The absorption of drugs was significantly increased by adding Azone in the gel ointment resulting in an approximate 3-fold increase in the parameters, Cmax and AUC. The percutaneous absorption of drugs from white petrolatum base was relatively lower than that from gel ointment. The plasma IND concentrations after a topical application of the gel ointments for 6 h (3.0 cm X 3.0 cm area, 1.0 g of 5% IND ointment) were over the therapeutically effective concentrations during 48 h. The bioavailability of IND after application of ointments was 9.1-27.8% for the gel base and 4.5-6.3% for the white petrolatum base. The in vitro penetration behavior of drugs using a Franz diffusion cell resembled the result of the in vivo absorption more closely. The relationship between the in vitro (the permeability coefficient and skin/ointment partition coefficient) and in vivo (Cmax and AUC) penetration parameters was linear and there was a clear correlation between both parameters.

Topics: Animals; Biological Availability; Calcium; Dimethyl Sulfoxide; Hexoses; In Vitro Techniques; Indomethacin; Kinetics; Male; Ointments; Propylene Glycol; Propylene Glycols; Rats; Rats, Inbred Strains; Skin Absorption; Thioglycolates