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

This week, we will look at "Supersaturation and Thermodynamic effects."

As we have previously discussed, the driving force for permeation is the thermodynamic activity of the drug (API) in the vehicle. Optimal transdermal drug delivery may be achieved from a saturated solution of the drug. However, when a drug solution is saturated at room temperature, upon application to the skin with a surface temperature of about 32�C, the drug solution may no longer be saturated.

It may be possible to further increase the thermodynamic activity in a formulation beyond unity by using supersaturated systems. As previously stated, for maximum permeation, the drug should be at its highest thermodynamic activity (i.e., in saturated solution [where the dissolved molecules are in equilibrium with solid]). However, this activity can be further enhanced when supersaturated states are formed. These systems may be unstable with material in excess of the solubility limit usually crystallizing out.

Supersaturation in a topical-dosage form can result from evaporation of a solvent or co-solvent from the system. Even though it may be uncontrolled and unpredictable, supersaturation of the API in the donor phase as the vehicle evaporates from the skin surface, it is a mechanism which is probably operating in many topically applied formulations.

For permeation, thermodynamic activity is the driving force, not concentration. Depletion of the drug in some cases may be problematic but can be overcome by the use of microcrystalline suspensions.

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 FDA and the University of Utah Drug Information Service (UUDIS) Differ on Defining "Drug Shortages"
2011 was a critical year in drug shortages. After several years of steady increases in new shortage reports, manufacturers, hospitals, and other stakeholders reported an unprecedented number of new drug shortages to the FDA; 251 in that year alone. The FDA and UUDIS's active shortage numbers are different because the two organizations use different definitions for what constitutes an active shortage; this is partly due to the organizations' objectives and partly due to the data that they have at their disposal.

• The UUDIS defines a shortage as a supply disruption that affects how the pharmacy prepares or dispenses a drug product or that influences patient care when prescribers must use an alternative agent.
• The FDA's definition of a shortage considers whether the combined supply from all manufacturers in a specific drug market meets historical demand patterns. In order to determine whether a market-wide shortage exists, the FDA first defines the relevant market.

The organizations ultimately have different objectives and different capabilities.

• The FDA's drug-shortage website is intended for the public as an indicator of active market-wide shortages. The list does not reflect the full scope of supply disruptions.
• The ASHP website is useful in helping pharmacists and clinicians manage the supply disruption at hand, whether the supply disruption is market-wide or not. The UUDIS provides information about which specific product presentations or versions are in short supply as well as evidence-based alternatives if no product is available.

Almost 600,000 Units of Saline Solution Recalled by Baxter
Baxter Healthcare has recalled nearly 600,000 units of 0.9% sodium chloride injection 500 mL; it is the sixth such recall of saline solution products by Baxter in the past 15 months. "Complaints were received of missing closures and/or leaks which may compromise product sterility," stated an FDA enforcement report about the latest recall, which Baxter initiated on March 18. The saline solution units in question were manufactured at Baxter's facility in Marion, North Carolina. Baxter recalled five other saline solution products in 2014.
http://www.medscape.com/viewarticle/842864

Hospira Gets Warning Letters for Its Plants on Four of Seven Continents
Hospira just received an FDA warning letter for a plant in Italy, meaning it now has plants tagged with warning letters on four of the seven continents: Europe, North America, Asia, Australia. However, the problem will be Pfizer's to deal with since it has struck a $15 billion deal to buy the sterile-injectable specialist. This letter raised questions about the plant's vial-stoppering procedures, its failure to look deeply enough into complaints, and its lack of controls for access to prevent data deletions from test equipment among other things.
http://www.fiercepharmamanufacturing.com/story/hospira-get-yet-another-warning-letter-one-italy-plant/2015-04-07

$5 Million in Tax Dollars Being Spent by NIH to Discourage Hipsters from Smoking
The government has spent millions of dollars in recent years to discourage tobacco use among hipsters through a program that recommends "styling your sweet mustache" and listening to music "no one else has heard of" as good alternatives to smoke breaks. NIH has awarded $5 million to the anti-smoking campaign since 2011, with the money going toward social events, ads, posters, T-shirts, social media, and more. Specifically targeted are hipsters, a subculture of young adults who are "focused on the alternative music scene, local artists and designers, and eclectic self expression," according to an abstract of the project.
http://www.washingtonpost.com/blogs/federal-eye/wp/2015/04/06/the-nih-is-spending-5-million-to-discourage-hipsters-from-smoking/

"Refusal to Fill"
West Virginia pain clinics are facing more scrutiny from health inspectors and federal authorities, so many pharmacists across the state are refusing to fill suspect prescriptions for pain medications. "Pharmacists are trying to do their part to stem West Virginia's pain pill problem," said Richard Stevens, executive director of the West Virginia Pharmacists Association. "Some pharmacies are taking the action of refusing to fill the scrips," Stevens said. "Unfortunately today, unlike the past, a pharmacist can't always dispense just because a physician has written a prescription for something. You have to use more professional judgment, and pharmacists are taking a second look at prescriptions for controlled substances." This increased scrutiny has led to some complaints filed by doctors and patients against pharmacists for not filling prescriptions. The West Virginia Board of Pharmacy, which licenses pharmacists, has investigated the complaints and found that the pharmacists were just doing their job.
http://www.wvgazette.com/article/20150405/GZ01/150409689

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Did You Know ...

�that it has been written "� the worker is worthy of his wages."? Pharmacists must be fairly compensated for all their professional activities, including dispensing, compounding, medication review, consulting, managing, etc.

Tip of the Week

If compensation is not received for each and every activity, it may not last long. Confirm that all the professional activities of each pharmacist are being fairly compensated for by patients, insurance companies, and other responsible parties.

Looking Back

A silky cheek,
Shaved smooth and clean,
Is not obtained
With a mowing machine!
     Burma Shave