Development and evaluation of matrix type transdermal patch of ethinylestradiol and medroxyprogesterone acetate for anti-implantation activity in female Wistar rats.
BACKGROUND
Medroxyprogesterone acetate (MPA), which increases high-density lipoprotein level, has not been used as a progestin in combination with estrogen in a transdermal patch to date. The aim of the research was to develop and evaluate a matrix-type transdermal drug delivery (TDD) system of a combination of ethinylestradiol (EE) and MPA for interception.


METHODS
The transdermal patch of EE and MPA was prepared using various film-forming polymers with and without n-dibutyl phthalate as plasticizer and with glycerol and sodium lauryl sulphate as penetration enhancer. All formulations were assayed using UV spectrophotometer by Vierordt's equation for EE and MPA.


RESULTS
The percentage cumulative release of F6 (optimized formulation) named as 'AGARPRU' was found to be 99.94%±1.25% and 69.99%±1.02% (mean±SD) through rat skin and 92.69%±2.22% and 53.51%±2.11% (mean±SD) through cadaver skin for EE and MPA, respectively. Pharmacodynamic studies of 'AGARPRU' in female Wistar rats showed 100% anti-implantation activity. The in vivo results showed prolonged T(max) of 36 h for both EE and MPA after transdermal administration compared to oral route (2 h). Moreover, the area under the curve of EE and MPA revealed an increase in bioavailability after transdermal administration as compared to oral route.


CONCLUSIONS
These findings suggested that TDD formulation aimed for postcoital antifertility activity has been successfully developed in female Wistar rats.
Delhi Institute of Pharmaceutical Sciences and Research, New Delhi, India.
Shyam Sunder
SS
Agrawal
Jatin Kumar
JK
Pruthi
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003281:Contraceptives, Postcoital / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004997:Ethinyl Estradiol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*
D003271:Contraceptive Agents, Female; D003281:Contraceptives, Postcoital; D004997:Ethinyl Estradiol; D017258:Medroxyprogesterone Acetate