No abstract

Based on t h e r e s u l t s o f simultaneous s k i n permeation and b i o c o n v e r s i o n p r o f i l e s , a Transdermal B i o a c t i v a t e d Hormone D e l i v e r y (TBHD) System was developed from t h e m i c r o r e s e r v o i r p a r t i t i o n -c o n t r o l l e d d r u g d e l i v e r y technology f o r t h e transdermal c o n t r o l l e d d e l i v e r y o f e s t r a d i o l prodrugs. Using t h e i n v i t r o s k i n permeation apparatus developed e a r l i e r , t h e k i n e t i c s o f r e l e a s e and s k i n permeation o f e s t r a d i o l prodrugs from t h e TBHD system and t h e r e g e n e r a t i o n o f e s t r a d i o l were s i m u l t a n e o u s l y s t u d i e d . R e s u l t s i n d i c a t e d t h a t a l l prodrugs a r e t o t a l l y converted by t h e e s t e r a s e t o e s t r a d i o l d u r i n g t h e course o f s k i n permeation. The r e l e a s e r a t e o f e s t r a d i o l was found t o be f i r s t enhanced by t h e e s t e r i f i c a t i o n o f t h e OH groups a t 3and 1 7 -p o s i t i o n and then decreased as t h e a l k y l c h a i n l e n g t h increased. The r a t e o f r e g e n e r a t i o n o f e s t r a d i o l from t h e prodrugs was found t o f o l l o w t h e o r d e r o f : d i a c e t a t e > v a l e r a t e > heptanoate > a c e t a t e > cypionate. Copyright 0 1985 by Marcel Dekker, Inc.1195 0363-9045/85/ 1 106-1 195 $3 .SO/O Drug Dev Ind Pharm Downloaded from informahealthcare.com by Washington University Library on 01/03/15For personal use only.