ABSTRACT
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.
Subject(s)
Contraceptive Agents/pharmacokinetics , Drug Carriers , Epidermis/metabolism , Ethinyl Estradiol/pharmacokinetics , Polymers/chemistry , Skin Absorption , Acrylates/chemistry , Administration, Cutaneous , Animals , Chemistry, Pharmaceutical , Contraceptive Agents/administration & dosage , Contraceptive Agents/blood , Contraceptive Agents/chemistry , Contraceptives, Oral, Combined/administration & dosage , Contraceptives, Oral, Combined/metabolism , Diffusion Chambers, Culture , Dosage Forms , Drug Combinations , Drug Compounding , Epidermis/drug effects , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/blood , Ethinyl Estradiol/chemistry , Ethinyl Estradiol/metabolism , Female , Humans , Hypromellose Derivatives , Methylcellulose/analogs & derivatives , Methylcellulose/chemistry , Norgestrel/administration & dosage , Norgestrel/analogs & derivatives , Norgestrel/metabolism , Oleic Acid/pharmacology , Organ Culture Techniques , Permeability , Polyurethanes/chemistry , Propylene Glycol/pharmacology , Silicones/chemistry , Skin Absorption/drug effects , Swine , Time FactorsABSTRACT
Film forming polymeric solutions as a novel approach for skin drug delivery were developed and characterized concerning their mechanical properties and water vapor permeability. They were developed by varying type and content of the film forming polymer as well as nature and content of the plasticizer. The resulting formulations were evaluated according to five criteria: drying time, cosmetic attractiveness, outward stickiness, integrity on skin (after 18 h) and viscosity. Among the 14 tested polymers 10 film formers yielded formulations with a positive evaluation in all five test criteria. Selected formulations were then investigated for tensile strength and elongation at break in vitro and for water vapor permeability in vitro (WVP) and in vivo (TEWL). Their mechanical properties determined in vitro were found to be not predictive for the flexibility and abrasion resistance observed on living skin. Similar to this, the results derived from the WVP and the TEWL methods were not in accordance with each other. Obviously, the investigated in vitro methods do not characterize the properties of the thin films on living skin satisfactorily. Nevertheless, the identified film forming solutions are a promising approach and will provide the basis for the further development of this novel dosage form.
