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penetrate

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    penetrate


    will it be ok to put yohimbine hcl powder in penetrate? some people have said you need a carrier with dsmo or something for topical y-hcl

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    Are you looking for local or systemic distribution?
    My The 1 LOG: http://anabolicminds.com/forum/steroids/254164-my-one-log.html
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    mostly local, to add to 6oxo formastane and 7oxo for anti-e fat burning and anti cortisol, i would be applying directly to prob areas. but it wouldnt be a bad thing to get systematic, but that would be a bonus.
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    I would go with a product like Ab-solved and add in your Y, 6-oxo & formestane. This way you will get local delivery. Penetrate is systematic.
    Recent log:http://anabolicminds.com/forum/supplement-reviews-logs/213350-lean-efx-refined.html
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    no kidding, you can add bulk powders to stuff like absolved. i did one time add 3 gm of formestane to aborbine jr. man you want to talk about tight pecs, wouldnt recommend it on a regular basis though. haha p.s. dont take a piss before you wash it off your hands.
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    Quote Originally Posted by thebigt
    haha p.s. dont take a piss before you wash it off your hands.
    OUCH!
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    Can I throw 7-oh-dhea powder into the penetrate?
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    Quote Originally Posted by psychospic
    Can I throw 7-oh-dhea powder into the penetrate?

    I would use a funnell rather than the throw method.
    Recent log:http://anabolicminds.com/forum/supplement-reviews-logs/213350-lean-efx-refined.html
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    ive had good luck with 7oxo and androstenetrione bulk powder mixed in penetrate. as a matter of fact one company sells it already mixed, using the same ing. as penetrate. but it is much much cheaper to make your own. just wasnt sure about the yohimbine.
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    Quote Originally Posted by bpmartyr
    I would use a funnell rather than the throw method.
    Classic
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    BP - what do you mean that Pentrate is systematic??

    Where'd you see that at?
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    Quote Originally Posted by bpmartyr
    I would use a funnell rather than the throw method.

    You mean I can't place the bottle acrosss the room while throwing powder at it???
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    Quote Originally Posted by jmh80
    BP - what do you mean that Pentrate is systematic??

    Where'd you see that at?
    From Advant's writeup:

    Percutaneous Delivery
    Though the terms are often used interchangeably in the literature, there are two distinct forms of drug delivery through the skin. The first, and most common, is "Transdermal Delivery" -- this involves a drug bypassing the skin barrier in order to be taken up into the bloodstream and distributed systemically (15). This basically does the same thing as oral delivery, but it is inherently time released and avoids first pass metabolism in the liver which can limit bioavailability and cause hepatotoxicity, so it is is advantageous for delivering many drugs.

    The second is "Percutaneous Delivery" (15)-- with this method, one bypasses the skin barrier, but with the purpose of delivering the drug to specific target tissues in the body, while AVOIDING uptake into the blood and subsequent systemic delivery. In the pharmaceutical realm, this has been pursued primarily for antibiotics and NSAIDS -- the former, to avoid destruction of systemic microflora (so-called "good bacteria"), and the latter to avoid hepatic recirculation, which is responsible for gastrointestinal problems.

    Unfortunately, the people who have developed most of the topical fat loss products thus far either do not know about or understand this difference or they do not understand its paramount importance in regards to adrenergic modulators such as yohimbine. With prohormones, systemic uptake and distribution is our goal -- they have poor oral bioavailability, so we are just trying to avoid the liver in order to get significant amounts in the bloodstream.

    However, with yohimbine and other adrenergic agents, oral bioavailabilty is not the issue -- at about 22%, it is more than adequate (16). We can readily achieve adequate blood levels with oral usage. The issue with these is that as we increase dosages (and thus blood levels) in order to increase distribution to adipose tissue to aid fat burning, we also increase distribution to the heart and CNS where we create numerous unwanted side effects such as rapid heart rate, high blood pressure, and overstimulation, which is particularly noticeable with exercises. Yohimbine is also used clinically to produce anxiety (17). Ideally, we want our drug to reach fat cells in high doses, without the dangerous side effects of high levels in the heart and central nervous system.

    So, how do we do this?? Unfortunately, it is easier said the done. Typically, drugs that penetrate the skin barrier and traverse the epidermis and dermis are rapidly taken up by the dermal microvasculature, where they are delivered systemically (just like with orals) -- this is well characterized in the literature (15,18,19) -- with direct tissue penetration being limited to 1-4 mm, which obviously is not exactly deep into the adipose tissue. And, considering that these substances have good oral bioavailability, if the dermal microvasculature is not taken into account, we end up with a product that not only does not localize delivery, it does not even deliver it systemically as efficiently as an oral would do. Considering these products cost far more than there oral counterparts, and could also be thought of as inconvenient in that you have to rub them on your body, any supplement developer who doesn't take dermal uptake into account has obviously missed the boat quite badly. And, guess what... Not one single product other than LipoDerm-Y does. And guess what else -- they probably are not going to because we have filed a use patent on the one carrier that has been shown in the literature to effectively accomplish this.

    Targeted Delivery
    Let's now take a look at the literature that supports the idea of tissue specific delivery of therapeutic substances. As mentioned previously, when it comes to targeted delivery, the pharmaceutical realm, and thus the literature, has primarily concerned itself with antibiotics/anti-fungals and NSAIDS. We will look at the three most important ones.

    Editors note: I am not going to give the name of the substance that has been shown to be effective as a vehicle for local delivery at this time. I may do so when the product comes out, as it has to listed on the label. Though we have filed a patent on it, there are many companies whom that will not stop from attempting to steal our intellectual property. They lack the intelligence and creativity to discover this sort of thing on there own (as well as the integrity to think such things matter) so they choose to make their money in this manner.

    The first study (19b) involved the NSAID indomethacin as the drug to be delivered. The drug was given orally (O) , topically without the "special delivery solvent" (WO), and with the "special delivery solvent" (W). The topicals were applied to the shoulder. For the first two hours after administration, concentrations of the drug in the deltoid (which is obviously even deeper than adipose tissue) were 5 times higher in W than in either O or WO. After 4 hours, it was 3 times as high, and by 8 hours it was still twice as high. Obviously, the formulation containing the "special delivery solvent" was vastly superior at delivering the drug to the target tissue. But what about delivery to unwanted tissues? If it was just a case of the "special delivery solvent" allowing more drug to cross the skin, this would not be a big deal -- we could just use more. What we also need is for a minimal amount of the drug to be delivered systemically, and once again, the "special delivery solvent" was shown to be superior. Maximal blood levels of all three compounds occurred at the 2 hour mark. W displayed levels about 1/3 that of O and 1/2 that of WO.

    If the significance of this is not clear, it basically means that localized delivery (what we want) per unit systemic delivery (what we don't want) for W was 15 times that of O and 10 times that of WO -- and this was to the muscle. Considering the adipose tissue is closer to the skin (which had levels 10 times as high as the muscle) and that the joint capsule (which is below the muscle) had levels 1/3 that of the muscle while with WO there were equal levels at the muscle and joint, the ratio of delivery to adipose tissue vs. systemic delivery for W is likely significantly higher.

    The second study (19c) utilized the antibiotic erythromycin as the delivery drug. Formulations for W and WO were identical to the above study. Oral administration was not tested. Exact counts of the concentration in muscle tissue was not reported, but the authors stated that after 4 hours, there was a major increase in the muscle mass below the site of application (I have contacted the authors to try to get exact data). Kidney and liver levels (indicative of systemic distribution) were significantly lower for W than WO -- about 1/2 for the former and 1/4 for the latter over 24 hours.

    The third study (19d) we will look at utilized the antifungal griseofulvin as the delivery drug and compared W with oral intake. The formulation for W was the same as the previous two studies. The accumulation of the active compound in the area of application for W was several hundredfold greater than that which accumulated in the organs, and brain levels were non-detectable, which is extremely important considering we are trying to avoid excessive CNS stimulation -- and all of this was a full four days after application. Compare this to oral delivery which showed concentrations that were approximately identical in all areas, which would be expected if systemic uptake occurred.

    Penetration Enhancement
    I think it should be clear from the previous studies that it is quite possible to achieve targeted delivery. However, if we cannot get adequate amounts of our substance past the skin barrier, it is a mute point. And, considering one of the skin primary purposes is as a water barrier (20), hydrophilic substances such as yohimbine do not readily pass through (21, 22,23). Thus, we need to turn to the topic of penetration enhancement (for a more thorough presentation, see my previous article Transdermal Delivery.

    Yohimbine HCl, with a LogP of about .75 (24), is fairly polar/hydrophilic, thus penetration enhancers should be chosen accordingly -- namely we want those which affect the polar route. This rules out many commonly employed penetration enhancers -- a fact many companies do not seem to be aware of. Since there is very little direct data on penetration enhancement with Yohimbine HCl, we will look at data when substances with similar physical properties were used.

    One promising chemical in this area is the terpene, l-menthol. Polar molecules undergo significant hydrogen bonding in the stratum corneum, which is the primary reason for their poor passage through the skin barrier (23). Because of the presence of a hydroxyl (OH) group, l-menthol should bond to these hydrogens (25), leaving our drug free to more easily traverse the skin barrier. And, indeed the data has supported this. It increased the permeability coefficient of mannitol 100 fold vs. control (26). In a study using Propranolol HCl which has a partition coefficient almost identical to yohimbine (Log P .74 vs. .75), it increased flux 1000 fold vs. control and also displayed the shortest lag time of all terpenes tested (25). This is in contrast to d-limonene, almost identical, structurally, to l-menthol, with the exception of lacking the afore mentioned hydroxyl group, which has been shown to much less effective for polar compounds (25, 27).

    A second chemical is laurocapram. It too has been shown to be quite successful with polar drugs (23,28,29) likely due to its increasing the water content of the lipid phase of the stratum corneum. In one study, it enhanced the flux of mannitol in a propylene glycol vehicle by over 350 fold (23). Unfortunately, it displays a significant lag time -- meaning it can take as much as 10 hours before it starts to work (30, 31, 32). Consider most of us shower daily, this is not acceptable.

    That brings us to n-methyl-2-pyrrolidinone (NMP). In combination with laurocapram, in a study using morphine hydrochloride, which has physical properties similar to Yohimbine Hydrochloride -- both polar molecules, molecular weight of 322 vs. 390 -- and is thus quite applicable, NMP was shown to significantly reduce the lag time (down to as low as 2 hours) as well as increase the rate of penetration for the drug as indicated by blood levels that were several thousandfold high than controls (32). In addition, it has been shown in several other studies to enhance penetration of polar molecules on its own, including a 256 fold increase with mannitol (23).

    Finally, we have also added glycerol, which provides dual functions. First, it helps to counter any skin irritation that might be caused by the alcohol carriers. This is due to its increasing the water content of the skin, and as alluded to in regards to laurocapram, this increase in water content has the added bonus of increasing penetration for polar molecules such as yohimbine (33, 34).

    Yohimbine vs. yohimbe
    Quite a bit of confusion seems to exist about the difference between Yohimbine and yohimbe. Yohimbine is the principal alkaloid from the herb P. yohimbe. However, there are 31 other yohimbane alkaloids that can be present in herbal yohimbe preparations. Some of these have different and unknown selectivities and potencies (and thus, effects) at the adrenergic receptors (35, 36) -- in addition, these preparations vary greatly from brand to brand and even from batch to batch, as no standardization for extraction exists. In fact, a recent investigation found that most over the counter preparations have little to no actual yohimbine (37). And, even in the more potent preparations, most people find a higher degree of undesirable effects with the herb vs. pure Yohimbine (due to the afore mentioned 31 other yohimbane alkaloids that can be present). With LipoDerm-Y, you are guaranteed 25mg of pure, pharmaceutical grade Yohimbine HCl per milliliter, without the added side effects from other alkaloids - thus, allowing safer, more reliable dosing.

    Dosing
    Because some people are unusually sensitive to yohimbine, I would recommend that one start with a small dose -- 3-4 squirts (50 mg) and then increase the dosage by 25-50mg each day until side effects become unacceptable. Dividing it into two doses would be ideal, but probably not necessary. In our beta testing, we have gone as high as 400mg/day without significant side effects. I have personally done this along with an EC stack, and the only time side effects were particularly noticeable was during workouts.

    Another thing to be considered when using yohimbine is that insulin blunts its lipolytic effects. Because yohimbine is not reaching the pancreas in significant amounts as it would with oral administration, insulin levels will not be as high for a given amount of carbohydrates, but they will still be elevated. Thus, it should ideally be used on a low-carb/ketogenic diet, or at the very least, one should do moderate aerobic activity for an extended period first thing in the morning on an empty stomach.

    Conclusion
    I think it should now be exceedingly clear that all topical fat loss products are not created equal -- and you should now be equipped to make an informed decision on which one to use. To sum up:

    The formulation should contain active ingredients that are significantly lipolytic rather than mere diuretics.
    The formulation should use yohimbine hydrochloride rather than the yohimbe herb.
    The formulation must not only include penetration enhancers, but they must be appropriate for polar a molecule.
    The formulation must avoid uptake by the dermal microvasculature or it will merely be an expensive, inefficient version of a pill.
    The formulation that meets these criteria is LipoDerm-Y.
    Recent log:http://anabolicminds.com/forum/supplement-reviews-logs/213350-lean-efx-refined.html
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    Alright, I don't feel like reading at this point.
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    Quote Originally Posted by jmh80
    Alright, I don't feel like reading at this point.
    Pansy!
    Recent log:http://anabolicminds.com/forum/supplement-reviews-logs/213350-lean-efx-refined.html
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    "He is not the least bit scared to be mashed into a pulp. Or to have his eyes gouged out and his elbows broken. His knee-caps split and his body burned away."
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    We are now the Knights who say..."Ekki-Ekki-Ekki-Ekki-PTANG. Zoom-Boing. Z'nourrwringmm.
    Recent log:http://anabolicminds.com/forum/supplement-reviews-logs/213350-lean-efx-refined.html
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    I could never understand what that last word was.
    I read the script looking for it, but gave up. The script is like 400 pages long.
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    Back to Penetrate...

    I'm going to put a bunch of DHEA, a few grams of bAET, 7-OXO/7-OH. Is this a good idea?
    The purpose would be cortisol reduction/mood/et al during PCT.

    Also, would Penetrate be ok for a hormone?



    I take it I wouldn't want to use it for a yohimbine/clenbuterol transdermal - since I didn't like the sides of oral clenbuterol...
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    Quote Originally Posted by jmh80

    Also, would Penetrate be ok for a hormone?

    Yes, it is ideal.
    Last edited by bpmartyr; 05-27-2006 at 07:41 PM.
    Recent log:http://anabolicminds.com/forum/supplement-reviews-logs/213350-lean-efx-refined.html
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    Quote Originally Posted by jmh80
    Back to Penetrate...

    I'm going to put a bunch of DHEA, a few grams of bAET, 7-OXO/7-OH. Is this a good idea?
    The purpose would be cortisol reduction/mood/et al during post cycle therapy.

    Also, would Penetrate be ok for a hormone?



    I take it I wouldn't want to use it for a yohimbine/clenbuterol transdermal - since I didn't like the sides of oral clenbuterol...
    Are you planning on running a TD soon Jmh?
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    Yeah - the cortisol formula mentioned above for during PCT.

    I'll add 2 caps of Lean Xtreme just to make sure.
    Maybe one if I start to see joint issues (or maybe none).

    Hormones - I don't own any of those except for DHEA...
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    bp-you are a friggin expert, 1ques, does it matter what local i add my stuff to or is just ab-solved good, also how do i go about mixing since most topical fat burners come in a tube?
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    Quote Originally Posted by thebigt
    bp-you are a friggin expert, 1ques, does it matter what local i add my stuff to or is just ab-solved good, also how do i go about mixing since most topical fat burners come in a tube?
    I am no expert.

    Turns out Absolved is discontinued so you can go with Lipoderm Y. It has Yohimbine and caffeine but you can add whatever else you may want in there. I guess.
    Recent log:http://anabolicminds.com/forum/supplement-reviews-logs/213350-lean-efx-refined.html
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    Quote Originally Posted by jmh80
    BP - what do you mean that Pentrate is systematic??

    Where'd you see that at?
    Its systemic vs a local (absolved, liposrem ultra...) meaning distributed throughout the body vs a region.
    My The 1 LOG: http://anabolicminds.com/forum/steroids/254164-my-one-log.html
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    I have been debating between transdermal 7-oh-dhea in penetrate or suspending it in olive oil. The problem is that one bottle of penetrate is way too much for my one gram of 7-oh-dhea. I am going to order one more gram as i just realized that I will be about 100mg short of what my PCT cycle calls for. Is there anything else I should mix into the penetrate that would be beneficial for my PCT but will not block my 7-oh-dhea absorption?
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    androstenetrione-6 oxo powder, formestane,forskolin, man the list goes on.
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    Quote Originally Posted by psychospic
    I have been debating between transdermal 7-oh-dhea in penetrate or suspending it in olive oil. The problem is that one bottle of penetrate is way too much for my one gram of 7-oh-dhea. I am going to order one more gram as i just realized that I will be about 100mg short of what my post cycle therapy cycle calls for. Is there anything else I should mix into the penetrate that would be beneficial for my PCT but will not block my 7-oh-dhea absorption?
    You don't have to use the whole bottle of penetrate. Just use 19ml of penetrate to the 1 gram 7-oh for 50mg/ml. Easy as pie.
    Recent log:http://anabolicminds.com/forum/supplement-reviews-logs/213350-lean-efx-refined.html
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    How about DHEA or bAET??
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    Quote Originally Posted by jmh80
    How about DHEA or bAET??

    I already bought DHEA caps. Didn't start thinking about this until after buying all my PCT supps. Havn't really given bAET a thought because I thought that it was so similar to 7-OH-DHEA that it would be too much of a similar thing.
    For PCT I will be running Nolva, clomid, DHEA, 7-oh-dhea, RXT or Inhibit-e, fenugreek and Anagen. If adding the bAET isn't too much then perhaps I will do it.
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    I think it's like $3 a gram. With 7-OH, I was only planning on adding 2 grams of each of them to my Penetrate/DHEA transdermal.

    Probably will be for 2 PCT's though...
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    sorry to hijack the thread, but what would be an optimal amount of DMSO to add to penetrate to make a hormone transdermal (test/EQ)? If we're talking V/V percentages that would be easiest to visualize.
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    Quote Originally Posted by mywetnightmares
    sorry to hijack the thread, but what would be an optimal amount of DMSO to add to penetrate to make a hormone transdermal (test/EQ)? If we're talking V/V percentages that would be easiest to visualize.

    I don't think it's really that necessary to add DMSO, but from what I've read 5-10% should do the trick. And that should be by volume.
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    Necessary, no, I've used it plain. But I want to add some for increased penetration.
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    Replies: 19
    Last Post: 07-30-2003, 08:18 AM

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