Introduction
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 prohormones
are usually taken 3-5 times daily.
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:
If you have any questions or comments regarding this article, please email
dvdtlsn@bulknutrition.com.
No part of this article may be reproduced in any form without the permission of David Tolson or Mike McCandless. 
