Spray-on birth control: New application eyed

Women now rely on contraception in such new forms as a transdermal patch and a vaginal ring. In fact, about 75% of readers participating in the 2003 Contraceptive Technology Update Contraception Survey say their facilities are offering these birth control options. What if women could get reliable birth control from a spray-on application to the skin?

The Population Council, a New York City-based research organization, has joined forces with an Australian firm in testing just such a delivery mechanism. The council is working with FemPharm Proprietary, a subsidiary of Melbourne, Australia-based Acrux Limited, in testing transdermal spray delivery of its proprietary progestin, Nestorone. The first study in women is slated to begin in 2004, with the clinical trial to be conducted at the Sydney Centre for Reproductive Health Research in Ashfield, New South Wales.

Nestorone is a very potent progestin, so its effects can be obtained with a very low dose, says Regine Sitruk-Ware, MD, the council’s executive director of contraceptive development. Nestorone falls into the category of 19-nor derivatives of progesterone, which are referred to as "pure" progestational molecules as they bind almost exclusively to the progesterone receptor without interfering with receptors of other steroids.1

Nestorone has strong progestational activity and antiovulatory potency with no androgenic or estrogenic activity in vivo.1

Council scientists are examining use of the progestin in various delivery systems, including vaginal rings, implants, and transdermal gel.2,3 A vaginal ring using a combination of the progestin with the estrogen ethinyl estradiol is set to enter Phase III trials in 2004, and gel application is in Phase II research, says Sitruk-Ware. Another Nestorone vaginal ring, delivering 50 mcg Nestorone per day, is being examined for use in breast-feeding women.3 Council researchers also are looking at use of the progestin in contraceptive implants; one such application has been eyed for postpartum women.4

"The advantage of Nestorone, because it is not active orally, if a very small amount passes in the milk to the infant, it is immediately destroyed and has no effect on the infant," says Sitruk-Ware.

Will spray stick?

Acrux has developed a unique transdermal delivery technology, which it has trade-named Metered Dose-Transdermal System (MDTS). It involves a unique delivery of small molecules, a "patchless patch," or an invisible, nonirritating depot of the drug in the stratum corneum, says Beverly Thomas, PhD, Acrux’s business development manager.

"The MDTS technology is based on a patented invention [U.S., Australian, and New Zealand patents issued, and patent is pending in 22 other countries], based on a remarkable observation that some of the commonly used sunscreens act as very effective skin penetration enhancers," explains Thomas. "Because of their safety, the regulatory path, especially for those molecules that are already approved via other routes of administration or as transdermal products already, is relatively simple."

The product is delivered via a spray applied once a day. The patient simply pushes a metering pump, similar to those used for nasal sprays, and sprays the formulation on the skin via a proprietary applicator. The alcoholic component of the formulation, which is a solution of the drug and the enhancer in alcohol, rapidly evaporates, and the drug and enhancer permeate the skin and form a drug reservoir in the skin.

Acrux has completed Phase II research with the MDTS application of estradiol in postmenopausal women and is in Phase IIb investigation with the MDTS application of testosterone for treatment of low libido in women, reports Thomas. (See company contact information in "Resources" at end of article.)

Testing takes time

While the concept of a spray-on contraceptive is intriguing, scientists must research the MDTS delivery of Nestorone to make sure it is an effective route of administration for birth control.

"The time line for the feasibility testing stage of product development typically takes approximately 18 months," explains Thomas. "This involves the formulation development work and resultant in vitro testing of formulations to identify the optimal formulation, which is then taken into a preliminary human proof of principle clinical study."

The proof of principle study demonstrates the systemic blood levels achieved from the formulation and is used to establish the exact dose needed to achieve therapeutic blood levels, she says.

If research proves positive, scientists hope that the result will translate into a contraceptive delivery system that is affordable, safe, cost-effective, reversible, and easy to use by women.

"We are eager to be a part of an endeavor that could result in the first-ever contraceptive delivered by a spray, which would give women and couples around the world another option for managing their fertility," says Sandra Arnold, vice president of corporate affairs for the Population Council.

References

1. Sitruk-Ware R, Small M, Kumar N, et al. Nestorone: Clinical applications for contraception and HRT. Steroids 2003; 68:907-913.

2. Brache V, Mishell DR, Lahteenmaki P, et al. Ovarian function during use of vaginal rings delivering three different doses of Nestorone. Contraception 2001; 63:257-261.

3. Massai R, Diaz S, Jackanicz T, et al. Vaginal rings for contraception in lactating women. Steroids 2000; 65:703-707.

4. Massai MR, Diaz S, Quinteros E, et al. Contraceptive efficacy and clinical performance of Nestorone implants in postpartum women. Contraception 2001; 64:369-376.

Resources

For more information on Acrux, contact:

  • Acrux Limited, 103-113 Stanley St., West Melbourne VIC 3003, Australia. Telephone: 61 3 8379 0100. Facsimile: 61 3 8379 0101. E-mail: info@acrux.com.au. Web: www.acrux.com.au.