Homebrewing with beta cyclodextrins

 Homebrewing with beta cyclodextrins

This article shows "real-life" pictures of homebrewing with HPBCD, cause our members liked to see how we do our experiments.

 The best tool available to make nasal and sublingual steroids are derivatives of beta cyclodextrins. The one that is most readily available is hydroxypropyl-beta cyclodextrin (HPBCD). (Note: Plain beta-cyclodextrin is of little use) In case you have not heard of these, cyclodextrins are cyclic oligosaccarides (sugars) that have a hydrophilic outer surface and a hydrophobic inner surface.(3) They can be thought of as a doughnut, with the center capable of having a steroid molecule stuck inside it. The hydrophilic outer surface makes the cyclodextrin soluble in water, and when it is combined with a steroid, it can make the poorly water soluble steroid soluble as well.(3) In addition to making steroids soluble, cyclodextrins have very other important properties that make them ideal for our purpose. Cyclodextrins are known to enhance steroid delivery through biological membranes.(3) The large CDs themselves are very bad at permeating biological membranes, but they deliver the steroid to the membrane, where it partitions into the membrane, leaving the CD on the outside of the membrane.(3) The conventional penetration enhancers like alcohols or polyethylene glycol act by disrupting the lipid layers of membranes.(3) That is a big source of irritation from the old formula, and this irritation can thus be avoided by the use of CD’s. Another advantage is, once administered, the steroid is rapidly absorbed. Nearly 95% of the steroid will be absorbed within 20 minutes. This also causes the need for multiple doses throughout the day.

 This system was developed because under normal circumstances, oral ingestion of pro-hormones and androgens result in destruction of the active ingredients as the tablets or capsules are metabolized by the liver. As a result, a large percentage of the ingested dose is converted into inactive end products that are excreted in the urine. Pro-hormone-poppers are designed to minimize destruction of the pro-hormones by bypassing the liver during "first-pass" metabolism. By enabling absorption of the active ingredients through non-gastrointestinal routes, such as under the tongue (sublingual) and in the buccal cavity (between the cheek and gums), the results is far higher blood androgen levels with Cyclo-Poppers than other pro-hormone products. In addition, the sublingual/buccal mode of administration is also safer that oral dosing .

 One of the primary issues concerning steroids and prohormones is that of optimal delivery. While most drugs and supplements are taken orally, there are a number of reasons why this method is largely ineffective with most prohormones. When taken orally, these compounds are extensively metabolized in the liver, making the dose used much larger than the amount that gets through. This may also place undue stress on the liver, especially with certain substances. Because of this, other delivery methods, such as transdermal, sublingual, and intranasal, have all become popularized, and each has advantages and disadvantages. This article discusses the compound hydroxypropyl-beta cyclodextrin (HPBCD), which can be used to facilitate prohormone delivery in a number of ways.

Cyclodextrins are a group of compounds that are commonly used in medicine to increase the aqueous solubility of drug substances by complexation [1]. Cyclodextrins are cyclic oligosaccarides, or sugars, which contain alpha-1,4 linked glucopyranose units (in the case of beta-cyclodextrins, seven of these units) in a truncated cone shape [2]. This results in a molecule that has an internal cavity that is hydrophobic and easily forms a complex with a steroid/prohormone molecule, while the outer surface of the cyclodextrin is hydrophilic, and this makes the complex easily dissolvable in water [2-4]. This renders prohormones much more bioavailable, and cyclodextrins are capable of enhancing nasal, sublingual, and transdermal delivery [5-6], among others. Moreover, cyclodextrins will cause much less irritation than other methods [3, 7].

The cyclodextrin of choice for prohormone delivery is HPBCD. When compared to other testosterone beta-cyclodextrin complexes, HPBCD was 1,533 percent more soluble in water, while another study found that HPBCD-steroid complexes were effective while beta-cyclodextrin-steroid complexes were not [4]. HPBCD also has an excellent safety profile.
 

Sublingual delivery

Sublingual delivery (administered under the tongue) presents an attractive alternative to traditional oral administration. Because of the limited surface area, the amount of prohormone that can be absorbed at one time appears to be 25 milligrams or less. However, when compared to oral delivery, even this amount is advantageous. One study found that a cyclodextrin complex containing 10 mg of testosterone delivered sublingually raised testosterone levels by 900% over baseline, with a 485% elevation at the two hour point. In contrast, even 200 mg of oral testosterone only raises levels by around 500% at the peak. A study comparing oral and cyclodextrin complexed 4-androstenediol also found that the sublingual version lead to a 261% greater increase in testosterone with one quarter of the dose, with the peak levels at 40 as opposed to 90 minutes. [4]

All in all, sublingual delivery is much more effective than oral for the amount used, but it does require more frequent dosing. Sublingual testosterone suspension (according to blood tests) has a half life of 60 minutes, non-estrified steroids 3 hours and short-acting (propionate) 8 hours.

Intranasal delivery

Intranasal delivery takes the trend of sublingual delivery even further. It is doubtful that more than 20 mg at a time will be absorbed using this method, and blood levels quickly spike 15 minutes after delivery and then dissipate to baseline by 90 minutes. Running a cycle using this method is impractical, as one has to dose up to 10 times daily. However, bioavailability is further increased – intranasal delivery has the highest bioavailability of all prohormone delivery methods, short of injection [7]. Additionally, intranasal delivery provides the most direct route to the brain [6, 7]. For these reasons, this method has become popular for pre-workout stimulant purposes. Many people report increased workout intensity from intranasal prohormones. DHT precursors are best suited to this purpose, although some other prohormones may make effective pre-workout stimulants as well.

Conclusion

HPBCD complexes can allow for a number of novel effective prohormone delivery methods. Each one has unique advantages and disadvantages. For further information, as well as information on creating your own cyclodextrin complexed prohormones, I recommend the following article:

 1.Eur J Pharm Sci. 2003 Oct;20(2):197-200. Driving forces and the influence of the buffer composition on the complexation reaction between ibuprofen and HPCD. Perlovich GL, Skar M, Bauer-Brandl A.
2. Int J Pharm. 2003 Sep 16;263(1-2):173-81. The effect of beta-cyclodextrins on the permeation of diclofenac from supersaturated solutions. Dias MM, Raghavan SL, Pellett MA, Hadgraft J.
3. Mind and Muscle Magazine Issue #9. Alternative Steroid Delivery Systems by Dazed.
4. Super Andro: Cyclodextrin Technology Shatters the Absorption Barrier by Patrick Arnold and David Garrett.
5. Int J Pharm. 2003 Mar 6;253(1-2):1-11. Mechanistic studies of the effect of hydroxypropyl-beta-cyclodextrin on in vitro transdermal permeation of corticosterone through hairless mouse skin. Shaker DS, Ghanem AH, Li SK, Warner KS, Hashem FM, Higuchi WI.
6. Int J Pharm. 2002 Oct 10;246(1-2):25-35. The effects of water-soluble cyclodextrins on the histological integrity of the rat nasal mucosa. Asai K, Morishita M, Katsuta H, Hosoda S, Shinomiya K, Noro M, Nagai T, Takayama K.
7. The Scoop on Intranasal Prohormones by Patrick Arnold

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On the picture below yoy see all ingredients of the formula below the saline (used by example to clean eyelenses) the PG the powders and the cyclodextrin.

I’ll outline a generic procedure for complexing non-esterified steroidal hormones with cyclodextrins.

Step One: In a clean glass container, dissolve 10 grams Hydroxypropyl-beta-cyclodextrin with 30 ml, sterile saline (like the stuff people use for their contact lenses and can be purchased in all pharmacies). Then chill the solution to under 40 degrees F in the refrigerator. This solution has to be cold or this won’t work.

Step Two: In a small glass bowl, add 1 gram of your favorite unesterified steroid (e.g. 4-androstenediol or stanozolol) to 5 ml propylene glycol and microwave about ten seconds until dissolved.  Propylene glycol is available by order at nearly any pharmacy and on the Internet.  Don't confuse it with ethylene glycol (antifreeze). Propylene glycol is virtually non-toxic.

Step Three: Mix 1.0 ml of the steroid/propylene glycol mixture with the cold cyclodextrin/saline solution and shake hard.  Repeat with each milliliter until all is mixed. 

You’ll have a clear solution of cyclodextrin/steroid complex with some propylene glycol in there too, but it’s not a real problem other than it might hurt a bit if you wanted to inject it.  Never heat the solution. It’s stable below 100 degrees F, but at high temperatures a precipitate forms. I'm not sure exactly how hot is too hot, but there’s no need to heat it anyhow.

Now, why would anyone want to do this other than to save some money by not having to go with Stanol-V of Stanozolic? Well, if you did this with stanozolol powder, you’d end up with a cyclodextrin complex of stanozol (basically Winstrol in a solution), which would be quite cool because not only could you inject this (provided you sterilized with a 0.22-u filter of some sort first), but because it’s a solution and not a suspension like Winny-V, you could actually use a 29-gauge insulin syringe with this and it would work quite well.

I’ve now given you a new way to use  stanozolol, in such a way that you’re no longer forced to solely use it orally. Good luck.

Cyclodextrins are known to enhance steroid delivery through biological membranes. The large CDs themselves are very bad at permeating biological membranes, but they deliver the steroid to the membrane, where it partitions into the membrane, leaving the CD on the outside of the membrane. The conventional penetration enhancers like alcohols or polyethylene glycol act by disrupting the lipid layers of membranes. That is a big source of irritation from the old formula, and this irritation can thus be avoided by the use of CD’s. Another advantage is, once administered, the steroid is rapidly absorbed. Nearly 95% of the steroid will be absorbed within 20 minutes. The reason why steroids,  need these delivery systems is because, when taken orally, a very high percentage of the steroid is deactivated by the liver, via first pass metabolism. This deactivation can be reduced many ways, including 17-alpha alkylation of the steroid, addition of esters and ethers to the 17beta hydroxyl group, using steroids that are unsaturated at the 1 position, or a combination thereof.

 Another strategy is to avoid the digestive tract all together. There are many ways to do this, but the most common delivery systems are transdermal, intranasal, and sublingual, and parenternal (injectable). The transdermal route is very well covered by the supplement industry, and from what I have seen and heard, some of these systems vastly surpass topical steroids compounded by pharmacists for hormone replacement therapy.

 The biggest advantage is that sublingual/buccal delivery, for the biggest part, avoids passage through the liver. And because halotestin is very toxic to the liver, you will understand why this method is preferred.

The UG lab that made the batch, analysed the batch (as they mostly do with new compounds) and saw to their surprise that the API's (raw powders) where switched. Their powder was no fluoxymesterone (Halotestin) but the very potent mibelorone.

An other experiment with tadelafil and vardenafil in hydroxypropyl-beta cyclodextrins it is clearly visible that both compounds react different on  24 hours stirring. Where the Vardenafil makes a clear solution, the Tadelafil makes a white creamy mess. This is done to fill the inner holes of the sugar with the active compounds that will transport the active ingredients through the membranes.  

An earlier experiment the formula is readeble on the bottle 80 ml saline + 2 gram Cialis powder with 18 gram HPBCD. Personally I prefer the Vardenafil that is much nicer and has a relative potency to sildenafil (Viagra) of 10.1 where as Tadelafil (Cialis) has a relative potency to sildenafil of 1.4. The downside of vardenafil is that it tastes very bitter, I've solved that problem..but won't reveil it !!

I need to make a living also..

Post your comments underneath, please. I would like to know if you can appreciate all my sweat...