Re: Why can't more drugs be delivered by transdermal patches?

Most drugs are soluble (they dissolve) in aqueous solutions. That would be okay for inside cells since the inside is mostly made up of water. However, the cell is surrounded by a membrane which is basically a layer of fat (lipid) with some protein embedded in it. For a drug to get across this layer of fat, it must be at least a little bit soluble in fat.

Chemically, it is rare for any chemical to be both soluble in water and fat (detergents are one example and why we use them for washing). Thus for a drug to get across the skin, it must go through cell membranes. This is true even if you eventually just want the drug to get to the blood. It still has to cross membranes to get there. In addition, with the skin, there is a dead layer of cells on the surface which is not only high in fat, but is dried out and has lots of connective proteins crosslinked together. This is an additional barrier. Thus, only a few drugs have the properties to be able to get through the skin into the general blood circulation. Also, the transdermal patch only covers a small area of skin. Even if a drug could get through the skin, it is going through only a small area of skin. This limits the rate and therefore the amount of drug that can be taken up in a given amount of time.

Finally, since only a little drug can get in through a small area of skin, the drug must not only have the chemical solubility properties I've described above, but it must be very "potent", that is it must work at a very low concentration. Potency is normally not a very important property of a drug (no matter what the drug company advertisements on TV tell you), but in the case of a transdermal delivery, potency is helpful since only a little bit of drug can be delivered.

There is a lot of research on this and other novel routes of drug delivery, by practically every major research drug company. Some chemicals can enhance delivery of drugs across the skin. One example is dimethyl sulfoxide (DMSO). It is (unfortunately) sold over the counter. It helps drugs gain entry basically by damaging the cell membrane to make it more permeable to other substances. This is generally not a very good idea. Not only does it damage the skin and other cells, sometimes permanently, but it also makes it difficult to control the amount of drug or other agent that passes through the membrane.