Transdermal contraceptive delivery system: Development, scaleup manufacturing and evaluations.

摘要

By employing various system designs and the use of skin permeation enhancers, a microreservoir drug delivery (MDD) type of transdermal contraceptive delivery (TCD) system was developed. The results from the in vitro skin permeation studies indicated that the TCD system delivers a low, effective dose of progestin and estrogen combination at a specific and controlled-rate for up to one week. This system was found both physically and chemically stable throughout a 26-week accelerated stability testing program. The results of a dermatotoxicity study also indicated that the TCD system caused very minor irritation and no histopathological changes to the skin. A continuous operation-type machinery and process was developed for scale-up manufacturing of the TCD system. Critical process variables were identified and tested for their effect on the quality of TCD system, such as weight variation, content uniformity, release and skin permeation rates. The quality of patches fabricated by this scale-up machine and process was found to be comparable to those prepared by manual thermal-compression process. Finally, the mechanism of skin permeation enhancement pertinent to this TCD system was elucidated by employing a bi-layer skin model. The skin permeation enhancers studied, including isopropyl myristate and n-decyl alcohol, were found to effectively increase the skin permeation rate as well as lowering the lag time of skin permeation for both 17