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Topical Transdermal Cannabis Salve Patch

How to make your own transdermal carrier:

AUG 15, 2013
Found this when looking for phlojel alternatives .... Curious what you guys think... Maybe Some of you can chime in


The current wave of local delivery topicals is based on the work of Marcel Nimni (Nimni, 1989, Nimni et al, 1997 & 1998) who developed and patented the trans-phase delivery system in 1989. The local delivery of products was reviewed by Guy and Maibach in 1982, and clearly demonstrated a number of products substantially increased localized subcutaneous concentrations of topically applied products. The products that best succeeded in doing this were those that were amphiphillic, that means they are soluble in both water and organic solvents (alcohols and oils for example).

Nimni's idea was simple : make the compound that needs to be delivered stable and amphiphillic and you can get substantial local delivery, with very minimal systemic delivery. This gives a predominantly localized effect, with minimum systemic (side-)effects. As research has previously demonstrated, benzyl alcohol can form micelles with organic ingredients, like most drugs used, in an aqueous environment. That means if you dissolve the products in benzyl alcohol you form an amphiphillic complex that can pass the skin and is taken up locally in the subcutaneous tissue to a great extent. Simply using benzyl alcohol and your product would already allow for local delivery, especially since benzyl is also a good penetrant of the skin due to its amphiphillic properties. But Nimni's system consisted of two phases. The second phase being a mixture of acetone and isopropanol. Both these solvents are very volatile and have both been shown to enhance skin permeation (Onken and Moyer, 1963). The idea is that the acetone and isopropanol make the skin more permeable and then evaporate, creating a sort of funneling effect that leaves the product entirely dissolved in the less volatile benzyl alcohol, which forms the amphiphillic micelles and carries the product across the skin. It transfers as it were, from one phase to another, and hence was dubbed the trans-phase delivery system by Nimni and his associates (Nimni et al, 1997).

Here are some good tips for people wanting to try this :

- All the ingredients, contrary to the current line of products using this technology are very cheap and very easy to get at any drugstore.

- The current line of products does not use acetone, even though research shows it to be the better product. they only use isopropanol. Using both however will create a much better and more stable effect. Nimni's idea was to use the two products with different evaporation rates to create more of a funneling effect whereby the acetone evaporates, leaving product funneled in a mixture of isopropanol and benzyl and then shortly after the isopropanol evaporates leaving it all in the benzyl.

How to make your own TPDS :

Take the product you wish to deliver, then add benzyl alcohol until it is entirely dissolved, even a few drops more (adequate benzyl for product). Then add a mixture of 4 parts acetone and 5 parts isopropanol, until you get the volume that gives you the desired concentration of drug per ml, and then apply as many ml as necessary to the site of application, twice daily.

Penetration enhancement

The rate limiting step, believe it or not, is still the permeation through the skin. The rate limiting step for that is permeation through the outer most layer, the stratum corneum. The stratum corneum can be depicted, for functional purposes, as a brick wall. The cells, called corneocytes, are the bricks, and in between is a continuous lipid layer that represents the mortar. Whether you traverse the stratum corneum through or between the cells, your penetration enhancers shoudl always exert an effect on the lipid layer. Almost all known permeation enhancers, with the exception of DMSO, work solely on the lipid layer. So that should not be a problem.

Here comes the tricky part, and another were manufacturers of existing products have fumbled a great deal. Penetration enhancers that do not evaporate (like acetone and isopropanol) also traverse the skin. They also dissolve organic compounds very well. That means if you volume of penetration enhancers is to great, a great deal of your product will traverse the skin dissolved in your permeation enhancer instead of in the benzyl micelles, and will be taken up systemic. Making all your efforts fruitless and rendering your product nothing more than a more expensive transdermal product. So when selecting permeation enhancers, select those that have the most effect in the smallest known volume. That is one area where most current products drop the ball.

Occlusion : the contradiction

Occlusion is often used with percutaneous absorption, whether it be local or transdermal, and has been shown to increase penetration of the skin. At first it was believed that this occured through the increase of water in the skin, but increased water was shown to have a minimal effect on lipid disorder in the lipid layers of the stratum corneum (Suhonen et al, 1999), so most likely it is a combination of both increased hydration and increased heat together, with either factor being relatively irrelevant alone.

The contradiction however is that occlusion is not an option with TPDS, since it would prevent evaporation of the first phase, resulting in part of the first phase traversing the skin, with product dissolved, resulting in systemic and not local delivery

This is yet another reason for an extremely small volume of penetration enhancers. If you cannot accomodate this, then it is best not to use PE's at all, as Nimni himself did, rather than risk affecting your primary delivery system.

Why Skulpt didn't work, but how you can make it work in your favour

Skulpt was an analog that was released for a while and then pulled again, that attempted to compete with aforementioned products, but despite all the obvious flaws in said products, failed at doing so.

The idea behind it was to use DMSO as a carrier instead of benzyl alcohol. DMSO is an incredibly potent penetration enhancer that affects both the lipid layers and the structure of the cells in between. It is also amphiphillic and easily builds up in subcutaneous tissues in high concentrations, and a good solvent for most organic compounds. So what was the problem ? Well, apparently DMSO does not function as a carrier. Instead it traverses the skin first and then pulls the product through, so to speak (kurihara-Bergstromm et al, 1987). Which is why skulpt failed.

Using a smaller dose of DMSO with the TPDS would also fail. First of all, when using DMSO as a solvent you need at least 50% for it to work adequately, while even 5% would already be enough to prevent TPDS from working properly. It traverses the skin and is a good solvent, so most of the product would dissolve in the DMSO and be lost systemically, rather than delivered locally through funneling to the benzyl phase.

Using DMSO however would benefit us greatly. Repeated application of percutaneous products results in less and less uptake with each use, and this occurs mostly through resistance in the lipid layers (Barry et all, 1972). So using a product that also works on the cells would definitely attenuate this decrease much much longer.

So how can we use DMSO ? Well the same researchers that found DMSO did not function as a carrier also tested an assymetrical model where they applied the DMSO first, and then the product. This resulted in a notably enhanced uptake of the compound WITH LESS DMSO THAN WHEN USING IT AS A SOLVENT. That means if you pretreat the skin with DMSO, and then apply your TPDS 5-10 minutes later, you have effectively created a product that blows any existing product out of the water.

But because you need less DMSO, and still have better and longer working penetration because of it, and don't require any of the large volume penetration enhancers often used, that screw up TPDS delivery, you save even more money (less DMSO, no other PE's and cheap TPDS in drug store) and get a much greater effect (DMSO stronger PE, TPDS works better).

Considering it was the PE's (and possibly greed) that made these initial formula's so extremely expensive, and that skulpt was also extremely expensive because of the high dose and high quality DMSO (you can choose for yourself now what quality DMSO you like) and both delivered relatively poor results, its basically a win-win situation.


You can no effectively make a local delivery formula in your kitchen that is ten times more effective, and ten times cheaper than any existing formula, and on top of that it allows you to look for cheaper ingredients, ingredients or combinations thereof that you deem more fit, or ingredients that couldn't be legally used by supplement companies.

And trust me, the inquisitive mind can easily improve on even this formula 5-10 times

Enjoy all homebrewers ...

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