Systemic delivery of active agents across the skin or mucosal membrane is convenient, pain-free, non-invasive and circumvents problems associated with the “first pass effect”. Such transdermal drug delivery is typically restricted to low-molecular weight drugs and drugs with specific lipophilic/hydrophilic balance able to penetrate the stratum corneum.
Transdermal drug delivery systems enable chemical modification of the barrier properties of skin to effectively and efficiently permit penetration thereof. Known drawbacks of transdermal delivery systems are, for example, the length of time needed for penetration, frequent dosing regimen, and the volume size of a transdermal composition needed to transdermally deliver a sufficient therapeutic amount of the active agent. Due to e.g. the need for such a large dose volume, the composition applied transdermally is inevitably maintained on the treated skin area for a long period of time, thereby exposing the active agent to be transdermally delivered to degradation processes and also exposing the immediate surroundings (e.g. clothing, spouses etc.) of the subject treated to the active agent.
Testosterone is an androgen, anabolic steroid which is primarily secreted in the testes of males and the ovaries of females, and in much smaller amounts by the adrenal glands. In men, testosterone plays a key role in the development of male reproductive tissues such as the testis and prostate, as well as promotes secondary sexual characteristics such as increased muscle, bone mass and hair growth. In women, testosterone plays a role in the development of pubic and axillary hair, sexual libido, bone density, muscle tone, and vitality. Testosterone is essential for health and well-being as well as the prevention of osteoporosis in both males and females.
Examples of known transdermal testosterone formulations for the treatment of e.g. hypogonadism are FORTESTA® (TOSTRAN®/TOSTREX®/ITNOGEN®) (ProStrakan Group plc), a 2% testosterone gel containing ethanol, propanol, propylene glycol, carbomer, triethanolamine, purified water, butylhydroxytoluene and oleic acid, TESTIM® (Auxilium Pharmaceuticals), a 1% testosterone gel containing pentadecalactone, acrylate, carbomer, glycerin, polyethylene glycol (PEG), propylene glycol, ethanol, tromethamine and water, and ANDROGEL® (TESTOGEL®) a 1% testosterone gel containing ethanol, isopropyl myristate, carbomer, sodium hydroxide and water.
U.S. Pat. No. 7,198,801 discloses formulations for transdermal or transmucosal administration of active agents, such as testosterone, containing an alkanol, a polyalcohol, and a monoalkyl ether of diethylene glycol. The formulations disclosed in U.S. Pat. No. 7,198,801 are reported to be substantially odor- and irritation-free as a result of the absence of long chain fatty alcohols, long-chain fatty acids, and long-chain fatty esters in the formulations.
As any product of technology at all times, also the latter formulations are not free of their own drawbacks and can further be improved upon. There is still a need for a transdermal formulation that delivers therapeutically effective amounts of testosterone in a controlled manner to subjects in need thereof, such formulation having high skin tolerability, efficient and regulated skin absorption, enabling daily doses having lower volumes and thus shorter administration regimens.