New Rasagiline Formulation May Allow Application to Skin

A new formulation of rasagiline, approved for Parkinson’s disease, may allow the therapy to be given by applying it to the skin.

The treatment’s new formulation was described in the European Journal of Pharmaceutics and Biopharmaceutics, in a study titled “Microemulsion-based gel for the transdermal delivery of rasagiline mesylate: In vitro and in vivo assessment for Parkinson’s therapy.”

Rasagiline works by blocking the activity of proteins that normally degrade dopamine in the brain, thus increasing brain levels of the neurotransmitter. An oral formulation of the medication is marketed as Azilect by Teva Pharmaceuticals.

Because the medication is metabolized fairly quickly within the body, patients usually need to take Rasagiline multiple times every day to get a therapeutic effect. Additionally, delivering Rasagiline orally can result in inconsistent amounts of the medication getting into the brain over time, since it needs to pass through the digestive tract first. Furthermore, oral medications may be difficult to take for people who have swallowing difficulties.

In light of these challenges, in the new study, an international team of researchers set out to create a formulation of rasagiline that can be delivered via the transdermal route — that is, applied to the skin and then absorbed into the body.

To develop this formulation, the researchers created microemulsions. Essentially, these are tiny droplets composed of water, oils, and other molecules that help the medication to be transported through the skin.

“Although no commercial ME [microemulsion]-based product for transdermal delivery is available, ME have tremendous potential for enhancing dermal and transdermal drug delivery,” the researchers wrote.

The researchers dubbed their formulation RSM-MEG, short for rasagiline maleate microemulsion-based gel.

After optimizing and characterizing the microemulsion-based formulation, the team tested its safety and effectiveness in laboratory models.

In rabbits, application of RSM-MEG to the skin did not cause any signs of irritation or inflammation after two days.

“This indicated safety of gel for skin application,” the researchers wrote.

In experiments using rat skin, the team demonstrated that RSM-MEG could deliver rasagiline through the skin more effectively than another gel formulation that didn’t use microemulsions (hydrogel), and could effectively deliver the medication into the bloodstream.

Finally, the team tested their formulation in a rat model of Parkinson’s induced by the pesticide rotenone. Treatment with RSM-MEG substantially improved motor function in this rat model, and RSM-MEG showed similar efficacy to orally administered rasagiline.

“These results demonstrate the potential of RSM-MEG for transdermal application as an antiparkinson’s therapy,” the researchers concluded.

The team is now planning further studies using pig and/or human skin to further validate these findings from rat models.