Alzheimers Disease

Transdermal delivery of drugs for neurodegenerative diseases.  The transdermal route possesses several advantages over other routes, such as avoidance of first pass effect metabolism and gastrointestinal side effects and/or metabolism, improved efficacy, and decreased toxicity.  Also, it presents a very appealing choice for the treatment of Alzheimer’s disease. Indeed, transdermal patches offer exceptional advantages for the AD  patients by reducing the pill burden, thus improving compliance. Moreover, a study involving 1059 AD patients’ caregivers revealed that 70% of them preferred rivastigmine patch over capsules. The preference was based on the patch ease of application and less interference with everyday life. In addition, there is an advantage to being able to see the applied patch as opposed to remembering if the patient has or has not taken their oral medication especially in patients who have impaired memory.

The objective of this research is to develop transdermal patches for delivery of drugs for some neurodegenerative diseases such as Alzheimer’s disease and multiple sclerosis. First, through investigating the effect of chemical penetration enhancers on the improving the transdermal  delivery of the drugs. Several penetration enhancers with different mechanisms of action at different concentration were compared to determine the enhancer with maximum enhancement ratio.

(Fig. 1)

Second, formulating the drug into a transdermal drug delivery system. Basically, there are two different types of patches; reservoir type and matrix type. Our focus is to formulate and characterize a transdermal patch of a drug for Alzheimer’s disease, which is available as oral tablets.

A drug in adhesive type of patch is formulated by dissolving the drug in an acrylate polymer matrix containing a penetration enhancer. For this purpose, several acrylate and silicon polymers were investigated to choose a candidate polymer that offers highest delivery of drug. In  addition, 10 different penetration enhancers were compared in terms of enhancement effect. The optimization of the formulation included a study of the effect of concentration of the API on the flux, and effect of addition of crystallization inhibitor. All permeation experiments were done using vertical Franz diffusion cell mounted with human cadaver skin.

(Fig. 2)

The developed patches are designed to be applied once daily to deliver the drug at the therapeutic level with minimum irritation.

Fig. 1: Using Franz diffusion cells to test the transdermal permeation of drug molecules with the
presence of different penetration enhancers

Fig. 2:
A schematic describing the process of developing and characterizing drug-in-adhesive patch.