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

This week, we will complete our series on "Formulating for Successful Transdermal Delivery."

Within the previous two weeks, we have listed four of six general rules on formulating for successful transdermal delivery. This week we will add the final two.

1. Select an appropriate drug
2. Drug flux considerations
3. Maintain saturation for maximum delivery
4. Possibly improve drug flux using formulation manipulation
5. A volatile/evaporating vehicle can increase finite dose delivery.

   The use of a vehicle/solvent that is volatile and evaporates after application to the skin will enhance drug concentration by producing a supersaturated solution and also may serve to modify the stratum corneum to aid drug passage. These vehicles may not be advisable for open lesions but tend to work well on intact skin. The "push" across the stratum corneum often results in a reservoir buildup of the drug for prolonged release.

6. After penetrating the skin, the drug molecule tends to continue moving, following a concentration gradient or an active process.

   In the treatment of many skin disorders, it is desirable for the drug to stay just below the skin surface with little or no drug entering into the systemic circulation. Localizing or targeting drugs to specific skin regions or layers is not currently feasible; however, there are a couple of approaches that can be considered. Placing the drug in a liposomal carrier may help hold the drug closer to the surface and may even result in the liposomes entering hair follicles for prolonged release of the drug. Also, the use of a solvent that will aid in rapid penetration to form a reservoir and alter the penetration capabilities of the surrounding tissue may result in holding the drug at the surface. Last, the use of occlusive lipid vehicles may result in a slow partitioning of the drug into the superficial layers.

Next week, we will look at another example of "Clinical Pharmaceutics."

Looking Ahead!

Coming up in the next issue of IJPC (being delivered this week) are articles on the following topics:

• Dry-heat Depyrogenation Ovens
• Compounded Testosterone Troches to Optimize Health
• Protocol for Blood Serum Eye Drops

News

Deceptive Pharmacy Practices and the Department of Defense
TRICARE, the Defense Health Agency, is moving aggressively to help its beneficiaries. Dr. George Jones, Chief of Pharmacy Operations, said that "Compounding pharmacies definitely have a role in medical care -- a very important role." But something has happened over the past five or six months where compounding pharmacies are charging unsupportable costs for some of these products, and expanding into areas where there is not good evidence to support the products' safety. Jones said that a new breed of compounding pharmacy is distorting some of the elements of this traditional process. Some of these pharmacies are using aggressive outreach programs to target TRICARE beneficiaries and collect their personal information. Then, they use it to bill TRICARE as high as $15,000 for a single, compounded prescription. Using aggressive marketing efforts, some of these pharmacies are trying to give compounding creams away, almost like door prizes, he added. Jones stated that "It will be an ongoing process, and we'll continue to make adjustments to ensure that we can provide access to legitimate compounds and still be good stewards of taxpayer dollars, and do what we can to help protect patients from some of these bad actors."
http://www.defense.gov/news/newsarticle.aspx?id=128809

TRICARE Now Screening Compounded Medications
Starting May 1, TRICARE pharmacy contractor Express Scripts began screening each ingredient in compound medications to ensure all are approved by the U.S. Food and Drug Administration. Under this new process, many patients who use personalized drug formulas still will have access to their medications, said Dr. George Jones, TRICARE's pharmacy chief. According to Jones and the Government Accountability Office, the number of compounded prescriptions filled by TRICARE has soared in the past several months, and costs now run 50 times higher than in 2004. Jones said Air Force Lt. Gen. Douglas Robb, Defense Health Agency director, issued a temporary hold last week on payments to some compound manufacturers while federal investigators examine allegations of fraud or illegal sales by these facilities.
http://www.militarytimes.com/story/military/benefits/health-care/2015/04/30/tricare-compound-medications-express-scripts/26634225/

Comparative Safety—Testosterone Dosage Forms
Increases in testosterone use and mixed reports of adverse events have raised concerns about the cardiovascular safety of testosterone, which is available in several different dosage forms with varying pharmacokinetics; injections cause spikes in testosterone levels, and transdermal patches and gels cause more subtle but sustained increases. The comparative cardiovascular safety of gels, injections, and patches has not been previously studied.

The investigators identified 544,115 testosterone initiators between the 3 data sets: 37.4% injection, 6.9% patch, and 55.8% gel. Testosterone injections were associated with a greater risk of cardiovascular events, hospitalizations, and deaths compared with gels; patches and gels had similar risk profiles. It must be mentioned that this study did not assess whether patients met criteria for use of testosterone and did not assess the safety of testosterone among users compared with nonusers of the drug.
http://archinte.jamanetwork.com/article.aspx?articleid=2293080

Life-threatening Errors with Flecainide Suspension in Children
Flecainide must often be compounded into a suspension when needed for infants and small children. Unfortunately, errors during preparation and dosing of the suspension have occasionally led to serious overdoses that resulted in cardiac emergencies and required immediate therapeutic intervention. ISMP first learned of a flecainide suspension-related error from a report submitted to ISMP in 2007. A 4-month-old infant had been receiving 8 mg twice daily as an 8-mg/mL suspension (1 mL per dose). When the dose was later increased to 10 mg, a suspension purported to be 10 mg/mL was compounded. However, the baby's mother complained that the suspension was too thick to withdraw from the bottle. The pharmacist asked the mother to return the suspension and elected to compound a 7-mg/mL suspension, instructing the parent to give 1.4 mL per dose. Due to a math error, this replacement suspension was actually compounded with 6 g (6,000 mg) of flecainide instead of 600 mg. Therefore, each dose represented 100 mg, not 10 mg. It is unclear whether the previous 10-mg/mL suspension may also have been prepared incorrectly. Efforts to standardize concentrations in both inpatient and outpatient pharmacies can help eliminate medication errors like those described.
http://www.ismp.org/newsletters/acutecare/showarticle.aspx?id=107

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Did You Know ...

�that it seems like the old saying "3 steps forward and 2 steps backward" is being experienced in pharmaceutical compounding?

Tip of the Week

Progress in patient care and professional pharmaceutical compounding can only be made when the profession "self-polices," and reports illegal and questionable activities to the appropriate authorities. By eliminating the negative activities, compounding will become more positive and influential as a profession and involved in patient care.

Looking Back

She put a bullet,
Thru his hat,
But he's had closer
Shaves than that!
     Burma Shave