Evaluation in vitro and in vivo of dimethicone transdermal therapeutic systems. Influence of propylene glycol on drug release.
Coumarin-containing transdermal drug delivery systems were studied in vitro for drug release and in vivo in rats for drug absorption. The matrix of the transdermal delivery system, dimethicone, was a commercially available silicone elastomer. The devices containing 1, 3 and 5% coumarin released in vitro 8.8 (87.4%), 23.4 (74.5%) and 31.6 mg (63.3%) of drug within 24 h. The device containing 5% coumarin was selected for further studies in which 5, 10, 20, 30, 50 and 70% propylene glycol was added. Up to 20% propylene glycol content did not change the amount released. The preparations with 30, 50 and 70% propylene glycol released 69.3, 73.6 and 87.9%, respectively. The 50 and 70% preparations were physically not acceptable. Only the preparations containing 5% coumarin without propylene glycol and 5% coumarin and 30% propylene glycol in the elastomer were evaluated in vivo. The area under the blood level-time curve of the propylene glycol-containing system was twice that of the device without propylene glycol. Blood levels were maintained between about 2 micrograms/ml and 5 micrograms/ml during the time the device was kept on the skin (24 h).
D000042:Absorption; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D003374:Coumarins / Q000008:administration & dosage / Q000378:metabolism; D005069:Evaluation Studies as Topic; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D011409:Propylene Glycols; D051381:Rats; D011919:Rats, Inbred Strains; D012828:Silicones / Q000008:administration & dosage*; D012841:Simethicone / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D012869:Skin Absorption
D003374:Coumarins; D011409:Propylene Glycols; D012828:Silicones; D012841:Simethicone