Reference

Long-term permeation kinetics of estradiol: V

Long-term permeation kinetics of estradiol: V. Development and evaluation of transdermal bioactivated hormone delivery system. Chien, Yie W.; Valia, Kirti H.; Doshi, Uday B. (Coll. Pharm., Rutgers, State Univ., Piscataway, NJ 08854, USA). Drug Dev. Ind. Pharm., 11(6-7), 1195-212 (English) 1985. CODEN: DDIPD8. ISSN: 0363-9045. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Based on the results of simultaneous skin permeation and bioconversion profiles, a transdermal bioactivated hormone delivery (TBHD) system was developed from the microreservoir partition-controlled drug delivery technol. for the transdermal controlled delivery of estradiol prodrugs. By using an in vitro skin permeation app. developed earlier, the kinetics of release and skin permeation of estradiol prodrugs from the TBHD system and the regeneration of estradiol [50-28-2] were simultaneously studied. All prodrugs were totally converted by the esterase to estradiol during the course of skin permeation. The release rate of estradiol was first enhanced by the esterification of the OH groups at positions 3 and 17, and then decreased as the alkyl chain length increased. The rate of regeneration of estradiol from the prodrugs was in the order: diacetate [3434-88-6] > valerate [979-32-8] > heptanoate [313-06-4] > acetate [1743-60-8] > cypionate [313-06-4].

Long-term permeation kinetics of estradiol: III

Long-term permeation kinetics of estradiol: III. Kinetic analyses of the simultaneous skin permeation and bioconversion of estradiol esters. Valia, Kirti H.; Tojo, Kakuji; Chien, Yie W. (Coll. Pharmacy, Rutgers, State Univ., Piscataway, NJ 08854, USA). Drug Dev. Ind. Pharm., 11(6-7), 1133-73 (English) 1985. CODEN: DDIPD8. ISSN: 0363-9045. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) A skin permeation system was utilized to study the kinetics of the simultaneous skin permeation and bioconversion of 5 estradiol esters. The equil. soly. of estradiol esters in the lipophilic silicone fluid and in hydrophilic PEG 400/saline soln. depended on the alkyl chain length of the esters. Estradiol 3,17-diacetate [3434-88-6] had a greater soly. in silicone fluid and a lower soly. in PEG 400/saline soln. than did estradiol 17b-acetate [1743-60-8]. The (skin/silicone fluid) partition coeffs. decreased as the alkyl chain increased in length. During the course of skin permeation, the estradiol esters were metabolized by esterase to regenerate estradiol. The rate of appearance of estradiol from the estradiol esters depended on the ester concn. on the stratum corneum surface and followed the order of: diacetate > valerate [979-32-8] > heptanoate [4956-37-0] > cypionate [313-06-4] > acetate. From the dermal uptake and metab. studies of estradiol esters, the 1st-order rate consts. for the metab. of estradiol esters were detd. The rate const. for the metab. of estradiol 3,17-diacetate to form estradiol acetate was ~22-fold faster than the rate const. for the metab. of estradiol acetate to generate estradiol. The enzymic hydrolysis of the ester group at the 17 position followed a 1st-order kinetic process, and the rate consts. varied with the variation in alkyl chain length.