Make your own local delivery topicals

[Big Cat]

Introduction

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.

Conclusion

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 ...

[MISTERDUDE]

Such awesome posts. And the articles you write for BB.com. Have you ever thought of writing for a magazine? There are many (well, not as many as there should be) hardcore bodybuilding magazine who would love suff like this, plus they would pay you the big $$$. Not to mention all your experience as a trainer....you may have thought of this already, but I just thought I would post it anyway. Thanks for all the time you put in here, I always learn a lot from everything you post.

[Big Cat]

Thank you, and although I'm always looking to make a buck, I'm not in this for the big bucks. I do this because I love it. If you found this post helpful, then that's already good enough for me.

I have had a few offers from magazines, but they always tell you you can only write so much, which usually means I need to dim it down, and I prefer writing about what interests me most. But when I get an offer that lets me write what I want, I'll take it

[musclemidget]

could you post a sample mixture of something like a topical 4-AD?

[Big Cat]

Well I don't know any solution rates for products in benzyl alcohol by heart, so that would be hard. But for instance if you wanted to create 6 grams of yohimbine Hcl, 8 oz worth (240 ml) then you would proceed by adding benzyl alcohol to your 6 grams of powderuntil it is completely dissolved and maybe 1 or 2 ml more, because since benzyl is the carrier, you want to make sure there is adequate carrier for your product. Then you add your acetone/isopropyl (4-5) mixture until the total reaches 8 oz.

If you are looking to deliver anabolic compounds, keep in mind that efficacy will vary depending on how deep the muscle is located. In an area with next to no fat, where the muscle is close to the skin, more product will build up, whereas in areas where more fat covers the muscle and distance is greater, less product will build up. The efficacy of local muscle building preparations is therefor largely dependent on the amount of fat in the place of application. Since this formula is more effective than current preparations, it will still deliver better results than existing commercial preparations.

For fat loss you can't go wrong, you will want to get rid of subcutaneous fat, which is always located right beneath the skin. Deepe subcutaneous adipose stores are harder to reach, but they respond better to lipolytic signals (Monzon et al, 2002) so fat loss should continue at an equal rate if skin doesn't become more resistant. Because of pretreatment with DMSO, resistance should develop to a much lesser extent than with current commercially available preparations.

[pogue]

BC, what is your opinion of using freebase compounds, vs ones with the hydrochloride still attached (ie: base yohimbine vs yohimbine hcl) when dealing with absorption rates? Do you think it makes much of a difference?

[Big Cat]

Not really, since the benzyl acts as a carrier. It all depends on how well the organic compound dissolves in the benzyl alcohol. To be correct you should test both and see which dissolves best and use that one. I'm guessing HCl would make it more hydrophillic and that may not be the best idea.

In any case, don't use long esters that make the product extremely lipophillic. Benzyl alcohol forms micelles in an aqueous environment, but not necessarily in an organic environment. The same thing that goes for the large volume PE's goes here, if it is too lipophillic more of it may be lost systemically. so for steroids and prohormones, definitely no esters.

[JustBrowsin]

stupid question perhaps, but what exactly is a local delivery topical?

[Rushi]

Originally posted by JustBrowsin
stupid question perhaps, but what exactly is a local delivery topical?

local delivery topicals are designed to administer a drug by a liquid based gel applied to the skin with the goal of having absorption/effects of the drug only in a specific area.

they're commonly used for localized fat loss in stubborn areas of the body such as the love handles or for localized androgen delivery for lagging muscle groups.

it is important to note that these products are more along the lines of site selective rather than site specific.

[musclemidget]

BC, do you think that a a combination of usnic acid and yohimbe hcl transdermal would be a good spot application fat loss gel?

[Big Cat]

There is so much potential, and so many good combinations. Yes, I do think that would be effective. Either way you'll get the best bang for your buck following these criteria :

1.Find drugs that are effective in the lowest doses
2.Find drugs that are synergistic
3.If at all possible, it helps if they dissolve well in benzyl alcohol. But most organic products do.

These criteria will allow maximum efficacy once saturation is reached.

[musclemidget]

well i know that yohimbe works well as a transdermal and i noticed that a few spray on fatlossproducts are out that have usnic acid in them, im just not sure how they are made and would like some assurance before i go out and spend alot of money trying to make a transdermal that wont work.

also, where can i get the benzyl alcohol, acetone and isopropanol that you say to use? local drug store?

[Big Cat]

yeps, any drug store carries them. And they don't cost all that much either. The benzyl acts as a carrier for organic compounds, all the fat loss aids discussed are organic compounds, so most anything will work. As long as the product exerts its effects on the fat cell directly, since it is delivered topically, it should have at least some effect.

[musclemidget]

im just wondering about the UA working as a transdermal. as i already said i know its in a few products on there, but that doesnt mean it works worth a ****. i dont feel like wasting perfectly good UA on something that wont work, so do you think itd have a good thermogenic effect in the application area?

also, would any spray bottle pretty much work to apply?

[Big Cat]

Originally posted by musclemidget
im just wondering about the UA working as a transdermal. as i already said i know its in a few products on there, but that doesnt mean it works worth a ****. i dont feel like wasting perfectly good UA on something that wont work, so do you think itd have a good thermogenic effect in the application area?

UA I believe works through uncoupling. SAT isn't particularly rich in metabolically active cells, so I doubt it would be the best product you can choose, but I think it would make a worthwhile addition nonetheless. I've seen commercial products use much worse, like specific beta3-agonists.

also, would any spray bottle pretty much work to apply?

Yes. Although having one that allows accurate dosing can help you figure out what dose you respond to, and help you cut costs even more.

[musclemidget]

Originally posted by Big Cat
Yes. Although having one that allows accurate dosing can help you figure out what dose you respond to, and help you cut costs even more.

any specific bottle?


ok, so all i need to get the benzyl alcohol, acetone, isopropanol, some yohimbe hcl powder (ill use the UA orally) and a spray bottle.

[Big Cat]

yes, and some DMSO for pretreatment would go a long way as well, since your skin becomes less permeable with each treatment, and pretreatment with DMSO would delay this and insure greater delivery across the skin.

[musclemidget]

alright peter, thanks for all the advice, i really appreciate it. i only have a few more, i promise .

what is DMSO and where can i get it? (drugstore also?)

are there any storing instructions once a topical is made (i.e. refrigerate, room temp, etc)?

heres what i think ill mix up to constitue a 4 fl. ounce/125 mL topical, critique it if you dont mind:

60 mL benzyl alcohol
4g yohimbe
34 mL isoproponal
28 mL acetone

anything else that you think would be benefical? colues forskolin maybe? maybe even 3-acetyl-7-oxo-dhea like absolved has?

i think i did the math right, but im not sure. i figure ill do the math w/the smaller numbers and simply double or triple them for larger doses.

[Big Cat]

Originally posted by musclemidget
alright peter, thanks for all the advice, i really appreciate it. i only have a few more, i promise .

what is DMSO and where can i get it? (drugstore also?)

Dimethyl Sulfoxide. Its one of the strongest and the most often used skin permeation enhancer around. Its been used for ages on the illicit circuit to transdermally deliver trenbolone. But apparently the stuff is perfectly legal since Patrick Arnold used it in Skulpt. More specific info is covered in the first post above. So you should be able to get it at a drug store.

are there any storing instructions once a topical is made (i.e. refrigerate, room temp, etc)?

Make sure the bottle closes well, don't expose to light or keep in a non-transparent or brown glass bottle, don't store at very high temperatures. Other than that it should be fine. The biggest problem is the volatility, so as long as you close it well and keep it away from hot or bright places it should store quite well.

[b]heres what i think ill mix up to constitue a 4 fl. ounce/125 mL topical, critique it if you dont mind:

60 mL benzyl alcohol
4g yohimbe
34 mL isoproponal
28 mL acetone

I'd just use the instructions as above. Drop the powder in, add benzyl until completely dissolved, mix up some 50/50 acetone and isopropanol in another bottle and then add that mixture until you get the desired concentration.

anything else that you think would be benefical? colues forskolin maybe? maybe even 3-acetyl-7-oxo-dhea like absolved has?

So many things. DHEA is a better option than 7-oxo-DHEA.

[musclemidget]

Originally posted by Big Cat

I'd just use the instructions as above. Drop the powder in, add benzyl until completely dissolved, mix up some 50/50 acetone and isopropanol in another bottle and then add that mixture until you get the desired concentration.

the instructions above said mix 5 parts isoproponal and 4 parts acetone to get the desired delivery per spray. thats what i was going w/.

Originally posted by Big Cat
[B]
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.

[Dai Kaioushin]

60 mL benzyl alcohol
34 mL isoproponal
28 mL acetone

Would this carrier be effective with 1T (similar to sytenchance) ?

[Big Cat]

Sytenhance uses the same formulation that was critiqued above, so it would work better than sytenhance. Provided sytenhance works at all of course, since muscle is a tissue located deeper than subcutaneous fat and with great variability from person to person and muscle to muscle.

This is already a serious improvement on the sytenhance formula, and i'm currently testing even far improved delivery systems, and I still wouldn't dream of calling a product uniformly fit to locally enhance muscle growth since it would work for one person, one muscle and might not work for another person and another muscle. Why do you think sytenhance was released by another company and not avant ?

[Dai Kaioushin]

Originally posted by Big Cat
Why do you think sytenhance was released by another company and not avant ?

Why do you ask me if I haven't asked this so far? Or wasn't it addressed direct to me?

Anyway thank you for the reply.



Daniel

[EAE]

Originally posted by Big Cat
Why do you think sytenhance was released by another company and not avant ?

I think Avant has dropped all their androgen containing products and have sold the formulas to Mike. They do sell "Gel #3" though, which is is Sytenhance minus the hormones.

[EAE]

Originally posted by Dai Kaioushin
Why do you ask me if I haven't asked this so far? Or wasn't it addressed direct to me?
Anyway thank you for the reply.
Daniel

I think it was just meant as one of those things that make you go "hmmmm."

[musclemidget]

Originally posted by Big Cat
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.

Originally posted by Big Cat
I'd just use the instructions as above. Drop the powder in, add benzyl until completely dissolved, mix up some 50/50 acetone and isopropanol in another bottle and then add that mixture until you get the desired concentration.

so which is it peter, 5 parts to 5 parts or 4 parts to 5 parts?

Originally posted by Big Cat

So many things. DHEA is a better option than 7-oxo-DHEA. [/B]

as a fat loss agent?

[Corbint]

So, a quick google for DMSO yields a site that sells a DMSO in 1lb tubs, and also roll-on types... But this paragraph is interesting :

"DMSO 99% purity. DMSO (Diamethyl Sulfoxide) is a solvent that has many uses and purposes. It is derived from wood pulp. It is a natural substance and is sold as a solvent. It is not sold for medicinal purposes! DMSO has many uses throughout the world."

NOT FOR MEDICINAL PURPOSES!

Wonder why.... Am I the only one that is worried by this?

[musclemidget]

Originally posted by Corbint

NOT FOR MEDICINAL PURPOSES!

Wonder why.... Am I the only one that is worried by this?

first, were using it merely to enhance skim permeability, not cure any disease.

second, youre talking to a bunch of bb'ers, we dont really care about something's intended use, but moreover its potential use. hell, half the guys on the boards take stuff meant to treat women's breast cancer (nolva), bull testosterone, and i myself have taken bird antibiotic pills in order to get some usnic acid.

so to answer, your question, you probably are.
p.s. i really wasnt trying to be a jerk, just merely explaining the lack of regard most of us have for ourselves.

[Corbint]

;-) good response... i found some more info on www.dmso.org, detailing that better permeation is achieved at a 70% to 90% pure DMSO compound, anything that has a higher purity doesnt work as good. interesting.... i can see it now, the next series of penis growth creams using DMSO to get nutrients into the wang!

bird pills, WTF!!!

[Big Cat]

Originally posted by musclemidget
so which is it peter, 5 parts to 5 parts or 4 parts to 5 parts?

I don't think it will make a real difference, but it is indeed 4:5. I stated it as 1:1 to simplify. The point I was making was that you can't determine the amount of either before you make it, it all depends on the amount of benzyl you will need for a given amount of product, then you top it of with the acetone/isoprop mixture.

as a fat loss agent?

No, for basting turkeys yes, as a fat loss agent.