Te-Yen Chien

Transdermal Dual-Controlled Delivery of Testosterone and Estradiol: (I) Impact of system Design

AbstractA multilaminate-type transdermal drug delivery (m-TDD) system was designed with the objective of delivering testosterone and estradiol simultaneously but at different daily dosage rates. To achieve such a dual-controlled transdermal delivery, skin permeation enhancer and permselective membrane were incorporated into the system. The results demonstrated that skin permeation enhancer, which is incorporated into the testosterone reservoir layer, and permselective membrane, which is added onto the drugreleasing surface of estradiol reservoir layer, can both alter the overall rate of skin permeation for both drugs. The skin permeation enhancer was observed to enhance the skin permeation rate of testosterone, while the permselective membrane was shown to reduce the skin permeation rate of estradiol. The addition of permselective membrane was observed to modify the release kinetics of estradiol from the matrix diffusion-controlled drug delivery to membrane permeation-controlled drug delivery. Other facto...

Transdermal Dual-Controlled Delivery of Testosterone and Estradiol: (II) Enhanced Skin Permeability and Membrane-Moderated Delivery

AbstractIn the second report of this series of investigations, series of alkanols, alkanoic acids and propyl alkanoates were evaluated for their potential as skin permeation enhancers for testosterone and estradiol delivered from a multilaminate-type transdermal drug delivery (m-TDD) system. Results indicated that permeation rates vary with the length of alkyl chain and the maximum enhancement effect is attained with alkanol having n=6–8 (n is the number of methylene groups), alkanoic acid having n=8–10, and propyl alkanoate having n=10–12. The enhancing effect of series of sorbitan esters and polysorbates on the skin permeation of testosterone was also studied; and the results indicated that sorbitan esters are effective skin permeation enhancer, while polysorbates are not. The effect of enhancer loading on the skin permeation rates of testosterone and estradiol, the barrier property of permselective membrane, the dosage rate ratio of testosterone/estradiol was extensively studied; and the effect of vari...

Transdermal Contraceptive Delivery System: Preclinical Development and Clinical Assessment

AbstractAn once-a-week transdermal (monophasic) contraceptive delivery system (TCDS), intended to be marketed in Asian countries, was developed at the Controlled Drug-Delivery Research Center, Rutgers, College of Pharmacy under the sponsorship of Sintong Chemical Industrial Co. Ltd. in Taiwan. This TCDS was designed to simultaneously deliver a low dose combination of levonorgestrel (LNG) and 17B-estradiol (E2) through the skin for the fertility regulation in female. In-vitro permeation study using human cadaver skin shows that 60.0 ± 9.42 mcg/day/10 cm2 of LNG and 28.8 ± 4.96 mcg/day/10 cm2 of E2 can be delivered from this system. The result of the one-week dermal toxicity study on 6 rabbits indicated the minimal potential of this TCDS to cause skin irritation. Histopathological examination revealed that this system causes only mild to moderate inflammation to the test animal which also showed no significant body weight change and sign of toxicity.A phase I bioavailability-dose proportionality clinical st...