First Contraceptive Spray Offers Advantages over the Pill

The Population Council (New York, NY) and Acrux Pharmaceuticals (West Melbourne, Australia) have reported positive Phase I results for the first contraceptive spray for women. Results indicate that daily, metered doses of the Population Council’s "Nesterone" hormone delivered with Acrux’s patented transdermal spray safely absorb into the skin and achieve the bloodstream plasma levels needed to block ovulation. Nesterone is a fourth-generation progestin that cannot be absorbed into the body by means of oral formulations.

After the spray is applied to the inside of the forearm, it dries quickly and forms a reservoir in the skin from which the drug is slowly released into the blood stream. Researchers believe that the technique offers more dosing options than oral progestin-only pills. "Because we form a reservoir in the skin that supplies drug at a relatively constant rate, leading to milder blood-level fluctuations than the pill, we expect that there will be greater flexibility with the timing of the dose using a metered-dose transdermal system (MDTS)," notes Igor Gonda, PhD, CEO and managing director of Acrux Ltd. One dose of the drug will not be entirely absorbed into the body within 24 hours, so scientists believe users will have greater flexibility over the timing of their doses. In contrast, oral contraceptives must be taken at approximately the same time each day to be most effective.

Researchers also speculate the spray method may have better user compliance compared with traditional oral and transdermal conceptive methods because it eliminates certain side effects. Because the transdermal spray completely bypasses the gastrointestinal route, side effects such as nausea (which makes some women skip oral doses) are eliminated. "The Population Council and Acrux are developing this new product because we believe that we will provide many women with an attractive choice of contraception that could be convenient, effective, and have no or few side effects," says Gonda.

In addition, formulation scientists use natural progesterone and estrogen derivatives rather than the modified, synthetic hormones that have been linked to rare cases of cardiovascular disease in oral- and patch-contraceptive users. According to Rgine L. Sitruk-Ware, PhD, executive director of product research and development at the Population Council, "The two natural hormones we use should improve the polarability and will have much less impact on the liver." Furthermore, the formulation may also be suitable for breastfeeding women because the compound cannot be orally absorbed.

As is the case with all companies that agree to collaborate with the Population Council, says Sitruk-Ware, Atrux will continue to develop the Nesterone MDTS regimen with the intention of one day marketing a certain volume of the regimen at a very low price for the public sector. Nesterone is particularly suitable for this purpose because the molecule so actively blocks ovulation, "we need microgram instead of milligram doses that you find sometimes in pills to be effective," says Sitruk-Ware. "Therefore, the total dose that you need will be less, so the cost is less. It’s a very convenient method."

Researchers are currently preparing the contraceptive spray for Phase II clinical trials. Acrux believes that creating larger quantities of the drug for later trials will not be problematic. "The MDTS technology uses standard pharmaceutical components and processes and is very easy to scale up," says Gonda.

-Kaylynn Chiarello