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

This week, we will look at "delivery through a repairing barrier."

The delivery of a drug through compromised skin is different than through intact skin and may present a problem for drug delivery. Skin conditions range from psoriasis and eczema to ulcers, herpes infections (warts and cold sores), and dermatophytoses (fungal infections), and the affected stratum corneum may allow for greater uptake of the active drug than when intact. As an example, the uptake of 8-methoxypsoralen into psoriatic plaques is greater than in intact stratum corneum, as plaques are largely devoid of the intracellular lipoidal content. Also, salicylic acid has been shown to be concentrated in the verrucae core and has been shown to be bound to the affected tissue. But, it is also possible that drug delivery can be reduced compared to normal tissue, for example, when the skin is thickened but intact (callus tissue).

As the skin barrier changes during therapy, the amount of drug delivery into the tissue also changes, and the dynamics of this process are complex. One has several options available to address this situation:

1. Alter the concentration of the active pharmaceutical ingredient (API) in the formula.
2. Leave the formula on the affected area either longer or for a shorter period of time.
3. Cover a larger or smaller area.

These simple approaches can compensate for the altered/reduced efficiency of drug permeation as the barrier changes and the stratum corneum restores its integrity.

Loyd V. Allen, Jr., PhD, RPh
Editor-in-Chief
International Journal of Pharmaceutical Compounding
Remington: The Science and Practice of Pharmacy Twenty-second edition

News

The British Medical Journal Says that NHS Doctors Should be Allowed to Prescribe Avastin
The British Medical Journal (BMJ) says that Novartis and Roche campaigned against study data supporting less expensive Avastin eye injections as a substitute for their own Lucentis. The BMJ states that Novartis and Roche intended to "undermine and divert attention" from trials pitting Lucentis against the less-expensive treatment. According to the Journal, Novartis even tried to sway doctors away from participating in the clinical studies. Lucentis brought in about $4.2 billion last year; Roche owns and markets it in the U.S., while Novartis sells it outside the U.S. In the UK, its use could release �102m a year for other patient services.
http://assets.fiercemarkets.net/public/bmjrelease.pdf

http://www.bmj.com/content/350/bmj.h1654

PBM's: And then there were ...
United Health Group's planned takeover of PBM provider Catamaran Corp will give the companies increased leverage in price talks with drug companies. The $12.8 billion deal comes at a time when others like Aetna and Cigna could pair up. Smaller companies like Health Net Inc., Molina Healthcare Inc., or WellCare Health Plans Inc. are also increasingly seen as takeover targets. Express Scripts Holdings Corp., the largest PBM and the only stand-alone PBM, may be forced to do a deal with a distribution company or pharmacy if margins become too tight, analysts said on Monday. The shifting competitive landscape could mean more changes for Humana Inc., which manages pharmacy benefits for Medicare. Humana had been reviewing the possible sale of that business, but ultimately decided to keep it.
http://www.reuters.com/article/2015/03/30/catamaran-ma-unitedheal-grp-idUSL2N0WW1IL20150330

Read and Interpret Carefully: Another Clinical Pharmaceutics Example
In December 2014, an article was published in PLoS ONE, with the title "Instability of Misoprostol Tablets Stored Outside the Blister: A Potential Serious Concern for Clinical Outcome in Medical Abortion." The results showed that after 48 hours, exposed tablets demonstrated increased weight, friability, and water content compared to controls and showed a loss of about 5.1% API and an increase in the inactive degradation products compared to controls.

This alarmed many because misoprostol is widely used in compounding. However, they did not read the article carefully. The tablets showing the loss were tablets that were removed from their protective blister packaging and stored exposed to 25�C/60% relative humidity out in the open! This is similar to what is called an "open dish" study where the drug is exposed to conditions with no protection. The properly packaged drug was used as the "control." Properly packaged, there should be no concern with the typical beyond-use dates assigned with compounded misoprostol preparations. What initiated this study involved hospitals that "opened" the blister packages a day or two prior to use of the drug.

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Book Review

Handbook of Drug Administration via Enteral Feeding Tubes
3rd Edition
White R, Bradnam V.
March 2015
Paperback; 752 pages; $74.99
Pharmaceutical Press

This book is published in conjunction with the British Pharmaceutical Nutrition Group. It furnishes background information for decision-making and provides over 400 drug monographs. Following discussions on feeding tubes, it presents information on types of flushing, restoring and maintaining patency, medication formulation, syringes and ports, interactions, and medication optimization. Following this are drug monographs with information related to enteral feeding of the specific medication. If involved in enteral administration of drugs using feeding tubes, this book should be in your library.

Did You Know ...

...that today we celebrate "Good Friday"? Good Friday is a Christian holiday commemorating the crucifixion of Jesus Christ and his death at Calvary. It is observed during Holy Week on the Friday preceding Easter Sunday, and may coincide with the Jewish observance of Passover. It is a widely-instituted legal holiday in many national governments around the world, including in most Western countries (especially among Catholic nations and the majority-Catholic countries) as well as in 12 U.S. states.

Tip of the Week

Worship with your family and friends this week. Many throughout the world are killed for what we take for granted every day�and Christians seem to be losing this freedom to worship.

Looking Back

Twinkle, twinkle,
One-eyed car,
We all wonder,
Where you are!
     Burma Shave