The Blurred Line Between "Topical" and "Transdermal", Part F

This week, we will look at more clinical implications of topicals and transdermals; "Formulation is more important than concentration."

What is the optimum drug concentration for efficient drug delivery through the skin? It is when the vehicle is saturated with the drug. There are very few cases in which the drug is so poorly soluble in the vehicle that rapid depletion of the drug in the formulation occurs. When the drug is in excess (suspended in the vehicle), as the dissolved drug moves from the vehicle into the skin, then it is replaced in solution by some of the suspended drug to maintain a saturated state.

Thermodynamic activity is what drives the drug across the skin, not concentration; so, adding higher and higher concentrations of drug is wasteful and does not add to the drug effect. In other words, "More is not always better." There are examples where commercial products have decreased drug concentration and maintained clinical equivalence.

Proper use of:

1. penetration enhancers within the formulation,
2. drug concentration,
3. overall vehicle acceptability and effectiveness,
4. area covered,
5. maintenance of skin health and hydration,

and other factors can lead to effective clinical results. Keep in mind that "More is not always better" and can lead to untoward effects in some patients. "Smart formulation development" may be less expensive for the patient and provide better patient care.

Next week, we will look at "What can be delivered through the skin?"

News

Note: It is interesting that combination therapy is so widely used in contemporary medicine but some of the PBMs are balking at paying for compounded preparations containing multiple ingredients. One only has to look at IV admixtures, TPN solutions, cancer cocktails, pain management, hormone therapy, etc. to see how widely used and necessary it is. Also, one glance at all the combination products on the market, both OTC and Rx, shows that combination therapy can be both safe and effective.

Multi-drug Cancer Cocktail Adds to Life
A three-drug cocktail of breast cancer drugs buys patients an extra 16 months of life and physicians have rushed to make it standard therapy. This combination includes two "magic bullet" drugs combined with standard chemotherapy and is used in patients with advanced HER-2 positive breast cancer. Debates are often held over changing practice for something that extends survival by a few months; so, 15.7 months is quite impressive. The cocktail includes Perjeta (pertuzumab), Herceptin, and docetaxel.
http://www.nbcnews.com/health/cancer/breast-cancer-cocktail-buys-more-year-life-n308426

Pricey Ophthalmics are Found to be Equally Effective
A government-funded study has found that three drugs, ranging in price from $50 to $1,950 a dose, are equally effective in treating many cases of vision loss caused by diabetes. However, the most expensive drug, Eylea (Regeneron Pharmaceuticals) was more effective for patients who had poorer vision before starting treatment. Lucentis, costing $1,200 a dose, and Avastin, at $50 a dose, were found to be essentially equivalent.
http://www.nytimes.com/2015/02/19/business/3-drugs-for-an-eye-disease-with-big-price-gaps-are-found-to-be-equals.html?ref=health&_r=0

Clinical Trial Problems Reported to FDA Seldom Published to Scientific Community/Public
A recent article published in JAMA reported that when the U.S. FDA inspections of facilities conducting human clinical trials uncover evidence of scientific misconduct or violations of trial standards, those outcomes seldom get passed along to the scientific community and beyond. In fact, for more than a decade, the FDA has shown a pattern of burying the details of misconduct resulting in a situation where nobody ever finds out which data is bogus, which experiments are tainted, and which drugs might be on the market under false pretenses.
http://www.oregonlive.com/pacific-northwest-news/index.ssf/2015/02/fda_in_jama.html

FDA's Final Inactive Ingredients Guidelines Criticized
FDA's final guidelines for ANDAs related to inactive ingredients, or excipients, have been criticized by the International Pharmaceutical Excipients Council of the Americas (IPECA). The organization says the document contains contradictory and vague information that can confuse ANDA sponsors and excipient manufacturers. The agency also puts too much emphasis on current data captured in the IID (Inactive Ingredients Database), which contains a lot of inaccurate, incomplete, and missing information according to the IPECA. For more information, read:
http://www.in-pharmatechnologist.com/Ingredients/IPEC-raises-concerns-over-FDA-guidance-related-to-inactive-ingredients

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Looking Back

When cutting whiskers,
You don't need,
To leave one half,
Of them for seed!
     Burma Shave