Testosterone undecanoate compositions

Abstract

The present disclosure is drawn to pharmaceutical compositions and oral dosage forms containing testosterone undecanoate, as well as related methods of treatment. In one embodiment, the oral dosage form can include a therapeutically effective amount of testosterone undecanoate and a pharmaceutically acceptable carrier. The dosage form can be formulated such that, when measured using a USP Type II apparatus in 1000 mL of 8 wt % Triton X-100 in water at 37° C. and 100 rpm, the oral dosage form releases at least 20% more testosterone undecanoate after the first 120 minutes than an equivalent dose testosterone undecanoate containing oral dosage form without the pharmaceutically acceptable carrier.

Description

FIELD OF THE INVENTION[0001]The present invention relates to solid testosterone undecanoate containing pharmaceutical compositions and oral dosage forms as well as associated methods of treatment. Accordingly, this invention involves the fields of chemistry, pharmaceutical sciences, medicine and other health sciences.BACKGROUND OF THE INVENTION[0002]The need for testosterone supplementation, often caused by testosterone deficiency, is a condition that can affect both men and women. Testosterone deficiency can be accompanied by a variety of symptoms including sexual dysfunction, reduced muscle mass and muscle strength, depressed mood, and osteoporosis. Male hypogonadism and female sexual dysfunction is characterized by a deficiency of endogenous testosterone production resulting in abnormally low levels of circulating testosterone. Currently, common testosterone therapy treatment can include administration of invasive intramuscular products, topical gels, topical solution and patches...

AI Technical Summary

Problems solved by technology

Male hypogonadism and female sexual dysfunction is characterized by a deficiency of endogenous testosterone production resulting in abnormally low levels of circulating testosterone.

There are challenges and drawbacks associated with each of these therapies.

For example, use of topical gels or topical solutions can result in accidental transfer of the active agent to others, such as children or partners.

Currently in the United States, there is no approved testosterone product available for the treatment of female sexual dysfunction and reduced sexual desire.

While oral is typically the most preferred and patient friendly route for administration, the oral delivery of testosterone as testosterone remains a huge challenge.

This is due to extremely poor bioavailability requiring very high dose as well as the short serum half-life requiring frequent dosing.

These problems with orally administered testosterone are primarily due to first pass metabolism.

Moreover, direct, oral delivery of testosterone is also known to cause enzyme induction resulting in potential drug-drug interactions.

However, liver damage including cholestasis, peliosis hepatitis, nodular regenerative hyperplasia, and primary hepatic tumors has been reported with use of methyl testosterone.

However, a huge drawback of the current state of the art oral liquid testosterone undecanoate formulations is that it has to be encapsulated in a capsule dosage form presenting it with limitations with respect to acceptable capsule sizes and related drug loading limitations due to testosterone undecanoate's poor solubility.

Such limitations present challenges with respect to patient compliance, because patients typically have to take multiple capsule units in order to get a sufficient dose to provide the desired efficacy.

Additionally, liquid capsule formulations tend to require more complicated and costly manufacturing processes and often require special storage and handling.

Moreover, liquid lipidic compositions can present oxidative instability challenges with respect to testosterone and its derivatives.