Testosterone transdermal delivery

Ainbinder, D., and E. Touitou. 2005. Testosterone ethosomes for enhanced transdermal delivery. Drug Deliv 12 1. 

These testosterone systems illustrate two different approaches to solve the problem of inadequate percutaneous absorption rate. In the former case, the patch must be applied to the body s most permeable skin site, the scrotum (which has been shown to be at least five times more permeable than ary other site). In the latter, the difficulty is resolved by creating a transdermal formulation which includes excipients to reduce barrier function. Neither solution is ideal scrotal application is clearly not preferred from a patient compliance standpoint on the other hand, permeation enhancers, by their very nature, tend to be irritating (and the more effective they are, the greater the irritation they provoke). This general problem, which presently limits the application of transdermal delivery, is now discussed in more detail. 

Advances in transdermal delivery systems (TDSs) and the technology involved have been rapid because of the sophistication of polymer science, which now allows incorporation of polymeric additives in TDSs in adequate quantity. Drugs with which transdermal therapy was pioneered include scopolamine, nitroglycerine, iso-sorbide dinitrite, clonidine, estradiol, nicotine, and testosterone [74],... 

Vesicle systems, described as ethosomes composed of phospholipid, ethanol, and water, have been shown to enhance the transdermal delivery of minoxidil and testosterone when compared to more traditional formulations (Fig. The quantities of drug penetrating... 

Shomaker, T.S., Zhang, J. and Ashbum, M.A. (2001) A pilot study assessing the impact of heat on transdermal delivery of testosterone . J. Clin. Pharmacol. 41, 677-682. 

Muddle, A.G., Longridge, D.J., Sweeney, P.A., Burkoth, XL. and Bellhouse, B.J. (1997) Transdermal delivery of testosterone to conscious rabbits using powderject (R) a supersonic powder delivery system . Proc. Int. Symp. Control. Release. Bioact. Mat. 24, 713. 

TRANSDERMAL DELIVERY SYSTEMS Attempts to avoid hepatic first-pass inactivation of testosterone have used chemicals called excipients to facilitate the cutaneous absorption of native... 

Current androgenic formulations for TRT largely are restricted to injectable formulations of testosterone esters, transdermal delivery formulations (scrotal or nonscrotal patches or gel), or buccal testosterone. Marketed injectable forms of testosterone esters (e.g., testosterone enanthate, propionate, or cypionate) produce undesirable fluctuations in testosterone blood levels, with supraphysiological concentrations early and subphysiological levels toward the end of the period before the next injection. These fluctuations provide an unsatisfactory benefits profile and, in some cases, undesired side effects. Skin patches provide a better blood level profile of testosterone, but skin irritation and daily application limit the usefulness and acceptability of this form of therapy. Oral... 

Misra, A., et al. (1997), Biphasic testosterone delivery profile observed with two different transdermal formulations, Pharm. Res., 14(9), 1264-1268. 

Yu, Z. Gupta, S.K. Hwang, S.S. Cook, D.M. Duckett, M.J. Atkinson, L.E. Transdermal testosterone administration in hypogonadal men comparison of pharmacokinetics at different sites of application and at the first and fifth days of application. J. Clin. Pharmacol. 1997, 57, 1129-1138. Zobrist, R.H. Quan, D. Thomas, H.M. Stanworth, S. Sanders, S.W. Pharmacokinetics and metabolism of transdermal oxybutynin in vitro and in vivo performance of novel delivery system. Pharm. Res. 2003, 20, 103-109. Marzulli, E.N. Barriers to skin penetration. J. Invest. Dermatol. 1962, 39, 387-389. 

Dosage forms with different mechanisms may bypass the organ of absorption, such as the GI tract. These include, for example, the transdermal testosterone patch. Also capable of bypass is the metered dose inhaler for pulmonary delivery of biological products such as a peptide or protein, with a propellant for lung absorption. 

Patches based on GL and pectin hydrogels were described by Mazzitelli et al. (2013). Hydrogels are formed by taking advantage of the different gelling properties of pectin and gelatin (i.e., ionic and thermal gelation mechanisms), and proposed as transdermal formulations for the delivery of testosterone to overcome the limitation of its low bioavailability due to liver pre-systemic metabolism. 

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