title: Episodic transdermal delivery of testosterone.
abstract: Film-forming lotions, precast films and adhesive patches containing testosterone (T) were prepared by compounding vinylic, acrylic and cellulosic polymers with a variety of excipients in order to achieve distribution of T in domains of heterogeneity within multicomponent matrices. The feasibility of this approach in achieving episodic transdermal delivery of testosterone (T) was investigated. Composition-dependent differences in extent of in vitro drug release and periodicity were observed. Representative formulations showing the most pronounced episodic T release in vitro were tested in female rats. Whereas intravenously administered T decayed exponentially, three maxima of T in serum were observed upon application of selected formulations. Thus, peak serum concentrations of 240, 36, and 29 ng/dL were observed at 0.2, 5, and 16.8 h after application of the preferred lotion formulation, and 89, 65, and 64 ng/dL at 1, 16.4, and 48.8 h after patches. Deconvolution, noncompartment pharmacokinetic analysis and multiple peak fitting also indicated episodicity. These results suggest the feasibility of using transdermal systems for pulsatile T delivery in a variety of clinical applications, including hormone supplementation and male contraception.
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, 226001, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Malik
authors.forename: K S
authors.initials: KS
authors.lastname: Venkatesh
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Dwivedi
authors.forename: Amit
authors.initials: A
authors.lastname: Misra
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption / Q000502:physiology; D013739:Testosterone / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D013739:Testosterone