Delivery of ethinylestradiol from film forming polymeric solutions across human epidermis in vitro and in vivo in pigs.
Film forming polymeric solutions may present an alternative to the common transdermal dosage forms such as patches or gels. To evaluate the potential of these systems for transdermal drug delivery the permeation of ethinylestradiol from four formulations with different polymers was tested across heat separated human epidermis. The formulation with the best results was then modified by incorporating chemical enhancers to further increase the efficiency of the delivery system. Finally, drug delivery from the developed film forming systems was compared to a commercially available transdermal patch in vitro as well as in vivo in pigs. Among the tested preparations the formulation with polyurethane-14-AMP-acrylates copolymer (DynamX) showed the highest ethinylestradiol permeation. The drug transport was further increased with the incorporation of oleic acid as penetration enhancer, especially when used in combination with propylene glycol. The enhancing effect of oleic acid/propylene glycol was concentration-dependent and increased disproportionately with rising enhancer content. The film forming solution showed a higher ethinylestradiol permeation through heat separated human epidermis than the commercial EVRA patch in vitro and achieved measurable plasma concentrations of ethinylestradiol in vivo in pigs. These promising results encourage the further development of film forming polymeric solutions as novel transdermal dosage form.
Zurdo Schroeder
Ines
I
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbruecken, Germany.
Franke
Patrick
P
Schaefer
Ulrich F
UF
Lehr
Claus-Michael
CM
D000179:Acrylates / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003270:Contraceptive Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D004304:Dosage Forms; D004337:Drug Carriers; D004338:Drug Combinations; D004339:Drug Compounding; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D009644:Norgestrel / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology; D009924:Organ Culture Techniques; D010539:Permeability; D011108:Polymers / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry; D019946:Propylene Glycol / Q000494:pharmacology; D012828:Silicones / Q000737:chemistry; D012869:Skin Absorption / Q000187:drug effects; D013552:Swine; D013997:Time Factors
D000179:Acrylates; D003270:Contraceptive Agents; D003277:Contraceptives, Oral, Combined; D004304:Dosage Forms; D004337:Drug Carriers; D004338:Drug Combinations; C511292:Ortho Evra; D011108:Polymers; D011140:Polyurethanes; D012828:Silicones; D019301:Oleic Acid; D009644:Norgestrel; D065347:Hypromellose Derivatives; D004997:Ethinyl Estradiol; C058665:Eudragit RL; D019946:Propylene Glycol; D008747:Methylcellulose