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

This week, we will look at "Formulating for Successful Transdermal/Topical Delivery."

Over the past several weeks, we have been discussing topical and transdermal formulations from various aspects. This week, we will consider formulating for a successful transdermal/topical preparation. Obviously not all drugs are suitable for application to the skin; however, many are suitable, and the list seems to be getting longer, as we are seeing more and more manufactured as well as compounded transdermal/topical products/preparations. Let's look at some general guidelines.

1. Select an appropriate drug
   
   Passive drug delivery seems to be appropriate for small molecules with good lipophilicity and adequate aqueous solubility. Generally, one looks at 300 to 500 Da, a log partition coefficient (octanol/water) in the range of 1 to 3.5, and an aqueous solubility in excess of 100 mcg/mL. A reasonable drug would have a "flux" in the range of about 1 mg/cm²/day, so covering an area of about 10 cm² would deliver about 10 mg/day. One must keep in mind that first-pass hepatic metabolism is avoided, so dosing may not necessarily follow oral-dosing regimens.
   
   
2. Drug flux considerations
   
   This data is sometimes available from published studies. If not, an estimate can be obtained using the Potts and Guy equation:

   Log k_p = 0.71 log P_(oct/water) -0.0061 MW - 2.74

   where k_p is the permeability coefficient (cm/h) through the stratum corneum, P_(oct./water) is the octanol/water partition coefficient of the permeant, and MW is the molecular weight of the drug.

We will continue next week with additional "general guidelines" for formulating a successful transdermal/topical preparation.

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News

Attix—Hundreds of Active Pharmaceutical Ingredients Recalled
Attix, a Canadian-based company that sources APIs from China and repackages them in Toronto, is recalling hundreds of bulk APIs sold in the past three years because the facility where they were packaged didn't adequately separate penicillin APIs from the rest of the APIs. Attix is recalling all nonpenicillin APIs (about 479) repackaged and distributed between January 5, 2012, and February 13, 2015. The FDA says the APIs were sold to "research" facilities and "compounding" pharmacies. http://www.fiercepharmamanufacturing.com/story/attix-pharmaceuticals-recalls-hundreds-apis-us/2015-04-30

Prices Soar after Companies Buy Rivals' Drugs
On February 10, Valeant Pharmaceuticals International Inc. purchased the rights to a pair of life-saving heart drugs. On the same day of that purchase, their list prices rose by 525% and 212%; neither of the drugs, Nitropress nor Isuprel, was improved. The big change was the drugs' ownership. A company spokesperson said, "Our duty is to our shareholders and to maximize the value of the products that Valeant sells." Branded-drug prices, since 2008, have increased 127%, compared with an 11% rise in the consumer price index.

See the figure below, which is self-explanatory.

States Push Bills to Require Pharma to Disclose Costs
A growing number of state legislatures are introducing bills in a bid to force the pharmaceutical industry to transparency." Tony DeLuca, a Democrat who chairs the Pennsylvania House Insurance Committee and who introduced one such bill earlier this week says, "Some of the sticker prices are outrageous. I'm hoping it achieves lower [healthcare] costs."

The efforts come as a national debate intensifies over prices for prescription drugs. The Pharma companies are on the defensive and argue pricey new medicines—notably, those for combating hepatitis C and certain rare diseases—represent good value for illnesses that would, otherwise, cost more to treat in the long run.
http://blogs.wsj.com/pharmalot/2015/04/24/angry-over-drug-prices-more-states-push-bills-for-pharma-to-disclose-costs/

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Did You Know ...

�that new SOPs have been added to the www.CompoundingToday.com website to assist in meeting the standards for PBM reimbursement certification? More on this next week.

Tip of the Week

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Looking Back

5-Star Generals,
Privates 1st class,
Show equal rank,
In the looking-glass!
     Burma Shave