Drug delivery to the human body is complicated business. It seems to the average consumer that they only have to take the pill and the API (Active pharmaceutical ingredient) magically does the work in the body. However, things are complicated when the API is not soluble. Drug delivery scientists spend significant amounts of time to formulate the preparation to achieve optimized absorption into the body. Ideally, you would like the excipient to be as neutral or inert as possible. In some cases, that has caused problems.
Consider the case of Althesin that was marketed by Glaxo in 1972 and was a mixture of alphaxalone and alphadone that was solubilized through Cremophor EL. This was an anesthetic that worked but was later withdrawn in 1984 not because the API did not work, but because the presence of the excipient caused the release of histamine and hypersensitivity reactions. Other drugs such as Propofol was also reformulated to a lipid emulsion and today serve as the gold standards for drug delivery and efficacy. Strangely, Cremophor EL continues to be used in cancer medications that utilize paclitaxel and it is thought that the effect of the drug is enhanced by the excipient. In todays treatment regimen of immunotherapy, wonder if the treating clinicians realize that excipients have such strong effects.
These days cyclodextrin’s are used as carrier agents and generally are safe but there are a few cyclodextrin moieties that show differential toxicity between dogs, cats and humans and you can read more about it in the context of Aflaxalone. So much more research is required when translating research from animal studies to humans.
One place drug delivery is practiced very well is by body builders who take creatine which is an amino acid important for building up muscle. Creatine is insoluble and there have been many methods to make it soluble. A micronized creatine creates very small particles that can be easily absorbed in the stomach. Other ways it has been solubilized is by making a solution. Body builders take this seriously and review the methods extensively.