Degradation of Cetirizine in alcohol vehicles!

N

nograde

New Member
Reaction score
3
Since my vellous sprouting growth rate seems to be diminishing i suspected degradation in my Vodka vehicle and googled a bit.

Look what I've found:

Contact of cetirizine should be avoided with alcohols having a molecular weight less than 100 as it results in a reaction with cetirizine, usually esterification, and thereby leads to instability of the dosage form....Cetirizine, under normal conditions of processing and storage is known to be reactive toward low molecular weight monohydric and polyhydric alcohols, which are conventionally used as solvents (such as methanol, ethanol, isopropanol and glycerin)
Click to expand...

I still cannot post links so look up in google: "Cetirizine Compositions site:freepatentsonline.com"

The reaction seems to be a "Fischer-esterification" between a carboxylic acid (Cetirizine) and alcohols. I tried to find out how much of an problem this could be in terms of intensity and speed of such a reaction in my own Cet-concoction, but I gave up. Maybe someone more knowledgeable in chemistry can help out?

- - - Updated - - -

Found another tidbit in US patent 6,171,618 "Combination dosage form comprising cetirizine and pseudoephedrine" from Pfizer Inc. (Maker of Zyrtec!)

The fact that alcohols and derivatives thereof such as esters are deleterious to formulations containing cetirizine is surprising in view of the fact that esters, for example glycerol esters, of cetirizine are difficult to make by conventional direct esterification methods. In view of the difficulty associated with direct esterification, it is surprising that cetirizine reactivity towards alcohols is such that extensive ester formation was observed when using processes to make dry solid formulations, such as tablets, in which cetirizine was exposed to glycerin or other alcohols in one or more steps.
Click to expand...

CET only in water for me from now on ....
 
Sparky4444

Sparky4444

Senior Member
Reaction score
44
..you know what, since I did my Vodka mix, things haven`t been the same...I think I am just going to drink the rest of my Grey Goose and go back to Tricomin and water too! Good find!!
 
L

Luxurious

New Member
Reaction score
1
Organic chemistry is so difficult to predict and remember correctly that it's very good you searched for that. It makes total sense as Fischer-esterification is one of the only things I remember about my organic chem class in college. Nice find
 
N

nograde

New Member
Reaction score
3
In the very same Patent from Pfizer there's actually an example on how NOT to do it, i.e. mixing Cetirizine and Alcohol and measuring what happens after some time ("Example 1"). They created a tablet which consisted of:

* Tablet Core 450mg (processed with 90mg Alcohol: Ethanol and Isopropyl Alcohol)
+ Membrane Coating yielding 585 mg (processed with 723mg Alcohol: mostly Ethanol and Isopropyl Alcohol, 45mg Glycerin)
+ Cetirizine/Pseudoephedrine Coating yielding 710mg (containing 10mg CET)
+ Taste Mask Coating yielding a total of 730mg for the whole tablet

Note that the alcohols have been marked as "volatile" and do (should?) not exist in the final product. Then they stored those tablets under different conditions and after three weeks they determinded CET degradation into "Cetirizine ester of glycerol" (CEG) relative to the CET peak amount.

Result:

* 50 Degree Celsius / 20% Humidity: 57% CEG
* 40 Degree Celsius / 75% Humidity: 43% CEG
* 5 Degree Celsius: 17% CEG

So only processing CET with alcohols does something that makes 40% of CET vanish at 40 Degree after three weeks. I would speculate that having Cetirizine in direct contact with alcohol like in my Vodka mixture would degrade CET even faster. Maybe after one week about half of the CET is gone! Haha, I was putting Vodka only on my scalp for several weeks ;-)
 
casperz

casperz

Experienced Member
Reaction score
25
Great find!

I'm going back to water/Cet this weekend, the last 10 days or so have been non productive in terms of any improvements.
 
B

bornthisway

Established Member
Reaction score
9
From IH forum 12/20:
According to the local chemist on the german board where this thing basically started ("Pilos"), water vehicle alone will not do anything, and alcohol based vehicle will not degrade cetirizine to any significance (basically from the sides of cetirizine in alcohol vehicle this can be concluded valid).

I'm not sure if the translation/interpretation of Pilos is correct, if it is, then I'm not sure whose right. :)

Pilos method was to dissolve in water, filter, add ethanol/ppg.
 
casperz

casperz

Experienced Member
Reaction score
25
Maybe the alcohol in the minoxidil has an effect?
 
C

cuprous

Member
Reaction score
16
Chromeo said:
According to the local chemist
Click to expand...

Sweeping statements like that are highly suspect unless they are backed up with evidence. Pfizer did studies with the application of cetrizine to rabbit skin and there WAS systemic absorption. See here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2751243/

Granted they mixed it with other things (not alochol).

Personally I think I feel a very, very slight numbness in the area where I have applied cet for a little while after application.
 
ladysmanfelpz

ladysmanfelpz

Established Member
Reaction score
24
So what are you guys doing here? I heard somewhere that mold and fungus allergies can cause hairloss and I am very allergic to molds and fungus. I cut up my pills of zyrtec in 1/4s so pills are 2.5 mg each and was thinking of micro dosing a little bit each day. Are you guys crushing up zyrtec, putting it into solution and applying to your scalp?
 
I

IdealForehead

Senior Member
My Regimen
Reaction score
3,025
Just want to revive this old (and brilliant) thread in light of the recent study @jamesbooker1975 made me aware of:

https://www.ncbi.nlm.nih.gov/pubmed/28604133

Looks like topical cetirizine can be considered an effective method. It's dirt cheap too. I was about to order some, until I saw this thread. So thanks to people of the past.

I need alcohol in my solvent for RU, minoxidil, and the other important components. So if cetirizine degrades in ethanol, it makes it almost impossible to be useful.

I wonder if similar second generation antihistamines like loratidine (Claritin) and fexofenadine (Allegra) would have the same problem. They should have the same mechanism of action. I will try to figure out if they are stable in alcohol or not...

If anyone knows, please chime in.
 
Last edited:
J

jamesbooker1975

Senior Member
My Regimen
Reaction score
1,032
In Argentina, there are drops available as an alternative for the pills form.
The drops contain 35 % Propylene glycol, Glicerine , sodium acetate and then sweeters and conservants. So, at least with PG it don't cause degradation.
 
I

IdealForehead

Senior Member
My Regimen
Reaction score
3,025
Solution!

Loratadine (Claritin) & Desloratadine (Clarinex) do not have any carboxylic acid group and thus should not be sensitive to Fischer-esterification (degradation by alcohol).

In fact, this fact sheet from Cayman Chem for Loratadine states wonderfully:

A stock solution may be made by dissolving the loratadine in the solvent of choice. The solubility of loratadine in ethanol and DMF is approximately 30 mg/mL and approximately 25 mg/mL in DMSO.
​
Pretty sweet.

For desloratadine, they state the solubility in ethanol and DMF is 30 mg/mL and 10 mg/mL in DMSO.

I will have to look further into the differences between these two and whether they should have the same mechanism of action as cetirizine in preventing balding.

So far, I can find the claim "Cetirizine was significantly more likely than loratadine to cause drowsiness and have a negative effect on motivation in one study of 60 patients with allergic rhinitis."

That fits with my experience. Cetirizine (reactine) knocks me out, while loratadine (claritin) does not. So maybe loratadine is a cleaner drug overall.

I also find this quote from this study:

Loratadine markedly, but not significantly, inhibited the sneezing response and reduced release of histamine, PGD2, and LTC4.
​
The whole point of cetirizine was to reduce PGD2 downstream from androgen receptor blocking.

It looks like loratadine should probably do the same but be stable in ethanol. I don't know that I'm going to bother with this right now, since I doubt anything could bind to my androgen receptors with everything I'm using to block them, and I doubt I could grow hair back any faster than I am now. But maybe down the road, I will try it out.
 
Last edited:
J

jgray201

Established Member
My Regimen
Reaction score
101
Didn't they use a topical solution/gel with alcohol in, in the topical cetirizine study? It didn't seem to lead to any degradation or loss in effectiveness.

IdealForehead said:
Solution!

Loratadine (Claritin) & Desloratadine (Clarinex) do not have any carboxylic acid group and thus should not be sensitive to Fischer-esterification (degradation by alcohol).

In fact, this fact sheet from Cayman Chem for Loratadine states wonderfully:

A stock solution may be made by dissolving the loratadine in the solvent of choice. The solubility of loratadine in ethanol and DMF is approximately 30 mg/mL and approximately 25 mg/mL in DMSO.
​
Pretty sweet.

For desloratadine, they state the solubility in ethanol and DMF is 30 mg/mL and 10 mg/mL in DMSO.

I will have to look further into the differences between these two and whether they should have the same mechanism of action as cetirizine in preventing balding.

So far, I can find the claim "Cetirizine was significantly more likely than loratadine to cause drowsiness and have a negative effect on motivation in one study of 60 patients with allergic rhinitis."

That fits with my experience. Cetirizine (reactine) knocks me out, while loratadine (claritin) does not. So maybe loratadine is a cleaner drug overall.

I also find this quote from this study:

Loratadine markedly, but not significantly, inhibited the sneezing response and reduced release of histamine, PGD2, and LTC4.
​
The whole point of cetirizine was to reduce PGD2 downstream from androgen receptor blocking.

It looks like loratadine should probably do the same but be stable in ethanol. I don't know that I'm going to bother with this right now, since I doubt anything could bind to my androgen receptors with everything I'm using to block them, and I doubt I could grow hair back any faster than I am now. But maybe down the road, I will try it out.
Click to expand...
 
I

IdealForehead

Senior Member
My Regimen
Reaction score
3,025
jgray201 said:
Didn't they use a topical solution/gel with alcohol in, in the topical cetirizine study? It didn't seem to lead to any degradation or loss in effectiveness.
Click to expand...

Thanks for that observation. Many aspects of that article make no sense to me, including their reporting and statistical analysis of results.

But this is yet another aspect I don't get. They say the treatment was:

"A galenic lotion composed of cetirizine 1%, 16% cyclo-silicone- pentamer, 96°C of ethyl alcohol applied once a day on the scalp."

https://www.yumpu.com/en/document/v...erapeutic-management-of-androgenetic-alopecia
​
What the hell does this mean? What does 96°C mean? Anyone know?

I feel like this article was written by monkeys and maybe it should be treated as such...
 
Last edited:
I

IdealForehead

Senior Member
My Regimen
Reaction score
3,025
So of loratadine and desloratadine, from what I can figure out, desloratadine is the primary active metabolite of loratadine and the most biologically active form. Your body needs to convert loratadine into desloratadine in the liver to get the antihistamine effect.

In this case, it probably makes the most sense to use desloratadine topically in high alcohol content vehicles. I'm looking into buying some now to play with. Again, can't see how it could hurt.

Regarding desloratadine:

In vitro studies have shown that desloratadine inhibits the release or generation of multiple inflammatory mediators, including IL-4, IL-6, IL-8, IL-13, PGD(2), leukotriene C(4), tryptase, histamine, and the TNF-alpha-induced chemokine RANTES.

https://www.ncbi.nlm.nih.gov/pubmed/11295678
​
That's at least theoretically the point. I'm ordering some to try and will post if anything interesting comes of it.
 
Last edited:
I

IdealForehead

Senior Member
My Regimen
Reaction score
3,025
You must log in or register to reply here.
Community platform by XenForo® © 2010-2023 XenForo Ltd.
Top