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

This week, we will look at some clinical implications of "topicals" and "transdermals"; "To occlude or not to occlude�."

It is well known that occlusive dressings applied to the site of application of a transdermal formulation increases drug delivery from most formulations. In fact, there have even been deaths reported from excessive application of lidocaine creams with occlusion to prepare the skin for various procedures in clinics.

Occlusion serves to hydrate the skin by preventing moisture from evaporating into the atmosphere; thus, it remains on or in the skin. The water content of the stratum corneum can increase up to 4-fold of the tissue dry weight, and drug (steroid) delivery can improve up to 100-fold when the skin tissue is covered. Other examples show lessor improvements in skin penetration but even a 10% to 100% improvement may be significant.

Occlusion does not always involve a plastic film or an occlusive ointment vehicle. In some cases, an infant's tightly fitting water-proof pants may occlude the area and increase drug delivery. Patch-delivery systems also take advantage of skin occlusion to enhance drug delivery.

However, the continued hydration of the skin may be problematic with microbial growth and irritation; these effects are usually reversible. An alternative is to use a volatile delivery vehicle. As the volatile delivery vehicle evaporates, it serves to increase the concentration of the drug to supersaturation so that increased amounts can penetrate into the stratum corneum.

To summarize, occlusion may be of benefit when enhanced drug penetration is needed over a prolonged period of time; it must be used cautiously and appropriately.

Next week, we will look at the "equivalence" issue between different formulations.

News

Drug Compounding Issues Addressed by the PCAC
The Pharmacy Compounding Advisory Committee (PCAC) of the FDA voted to add 25 drugs to the list of drug products that may not be compounded under the exemptions provided by the Federal FDC Act. These drugs have been withdrawn or removed from the market as a result of their components having been determined to be unsafe or ineffective. The list includes:

• Alatrofloxacin mesylate (all drug products)
• Aminopyrine
• Astemizole
• Bromfenac sodium (except ophthalmic solutions)
• Cerivastatin sodium
• Chloramphenicol (all oral drug products)
• Cisapride
• Esmolol HCL (all parenteral drug products that supply 250 mg/mL of concentrated esmolol per 10-mL ampule
• Etretinate (all drug products)
• Gatifloxacin (except ophthalmic solutions)
• Grepafloxacin
• Methoxyflurane
• Novobiocin sodium
• Pemoline
• Pergolide mesylate
• Phenylpropanolamine
• Propoxyphene
• Rapacuronium bromide
• Rofecoxib
• Sibutramine hydrochloride
• Tegaserod maleate
• Troglitazone
• Trovafloxacin mesylate
• Valdecoxib

Also included are:

• All extended-release drug products containing oxycodone hydrochloride that have not been determined by the FDA to have abuse-deterrent properties
• All drug products containing polyethylene glycol 3350, sodium chloride, sodium bicarbonate, and potassium chloride for oral solution, and 10 mg or more of bisacodyl delayed-release tablet

They also updated the current entry of Adenosine phosphate to state, "All drug products containing adenosine 5'-monophosphate (AMP), adenosine 5'-diphosphate (ADP), and adenosine 5'-triphosphate (ATP)."

Regarding the Bulk Drug Substance List:

Added:

• Cantharidin
• Diphenylcyclopropenone
• Squaric acid dibutyl ester
• Thymol Iodide

Denied:

• Piracetam
• Silver Protein Mild

http://www.medscape.com/viewarticle/840346

Note: The list to which the above may be added is available at:
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=216.24

New App Tracks Drug Shortages
The FDA has released a new smartphone app to keep healthcare officials and the public updated on shortages. It is available for free in the Google Play store for phones running Google's Android and the Apple App Store for Apple's iPhones. Reasons given for drug shortages include quality and manufacturing issues, production delays, and discontinuation of less-profitable drugs.
http://www.cbsnews.com/news/fda-smartphone-app-tracks-medication-shortages/

Heat and the Swine Flu Vaccine
The makers of the nasal spray version of the flu vaccine say now they know why it has failed to protect young U.S. children against swine flu—fragile doses got too warm. FluMist vaccine works well for most flu strains, but small studies found it didn't work very well against the swine flu bug that first emerged in 2009 and has returned each year since but wasn't a big player this flu season.

The issue was apparent last year when swine flu was behind most illnesses. Company officials said they investigated and concluded that the swine flu part of the vaccine is "unusually" sensitive to heat. Flu vaccine is refrigerated but is allowed to be out at room temperature for up to two hours during distribution; when left out on hot days, it was least effective because it degraded and lost potency.
http://hosted.ap.org/dynamic/stories/U/US_MED_FLU_VACCINE?SITE=AP&SECTION=HOME&TEMPLATE=DEFAULT

Public Citizen Calls for Pulling Ketoconazole Tablets off the Market
Public Citizen, a consumer safety group, has called on the FDA to pull ketoconazole tablets off the market; they say that there are safer medicines that do not carry risks of liver damage. Ketoconazole, first approved in 1981, has long carried a boxed warning about potentially fatal liver damage.
http://hosted.ap.org/dynamic/stories/U/US_ANTIFUNGAL_DRUG_SAFETY?SITE=AP&SECTION=HOME&TEMPLATE=DEFAULT

Smart, Self-Destructing Syringes
The WHO has called for the worldwide use of needle syringes that self-destruct after a single injection. The "smart" syringes are a response to a problem that medical authorities have recognized for decades—the frequent reuse of disposable syringes. It has been estimated that 25% of the 18 billion medical injections performed worldwide each year are done with dirty needles, and unsafe injections cause as many as 1.7 million new hepatitis B infections annually, 315,000 hepatitis C infections, and 33,800 HIV infections.
http://www.washingtonpost.com/blogs/wonkblog/wp/2015/02/24/why-it-took-so-long-for-the-world-to-start-using-smart-self-destructing-syringes/

Book Review

Applied Pharmaceutics in Contemporary Compounding
3rd ed.
Shrewsbury RP, PhD
Morton Publishing; Englewood, CO
Paperback. 454 pages. 2015.
Available at: amazon.com

This third edition continues the high standards set in this book incorporating substantial changes that have occurred in the "compounding world." The 32 chapters are logically divided and presented using a reasonable and practical approach to the broad world of pharmaceutical compounding. Pharmaceutical compounding is based on pharmaceutics, and the presentation of the sciences and the examples of the application of the scientific principles is very, very useful. This book is highly recommended and should be a part of every compounding pharmacists' and pharmacy students' libraries.

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Did You Know ...

�that with all the changes going on in the "compounding world," it is sometimes difficult to determine what is "real," "factual" or simply "opinion," or even "misrepresentation"?

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