Episodic Transdermal Delivery of Testosterone
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- 作者：Ritu Malik ; K. S. Venkatesh ; Anil Kumar Dwivedi ; Amit Misra
- 刊名：Molecular Pharmaceutics
- 出版年：2012
- 出版时间：June 4, 2012
- 年：2012
- 卷：9
- 期：6
- 页码：1537-1543
- 全文大小：306K
- 年卷期：v.9,no.6(June 4, 2012)
- ISSN：1543-8392
文摘
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.