Cyclizine HCl 50mg tablets and cyclizine lactate

[CretiNation]

Ok so as we all know potentiating opioids is great/fun/wow/amazing/ZAM! we also know that cyclizine hcl is available OTC in the US as 50mg tablets (y'all) know the trade name(s) and has round a 1mg/ml h2o solubility. I have been doin' a bit of research (clear the way etc) and came across this link:

http://www.uspbpep.com/usp29/v29240/usp29nf24s0_m20950.html

now, my goal here (i hope this is allowed please let it be allowed, it ain't synth!) is to extract the not-so-h2o-soluble cyclizine hcl then turn it into it's very h2o soluble cousin: cyclizine lactate. after finding a few different contradictory information the link i just posted used a procedure to identify cyclizine + h + cl is in cyclizine hcl (?? correct if wrong). now i ain't a chem buff i have a bs in neuroscience and wanna go for my phd in the neuro/pharmacology ANYWAY; i have a bit of organic chem experience.

to extract the cyclizine hcl from tablets is as follows:

1.) crush tablets and mix with a small amount of cold h2o to get rid of the starch. the rest of the inactive ingredients'll* have to hang on for the ride.

2.) for every 500mg of cyclizine hcl used add 10ml of a mix of 3 parts MeOH and 2 parts H2O, warming if necessary. apparently until the c. hcl has dissolved. i'm not sure how i'll indicate THAT so let's filter out everything that didn't dissolve and don't discard... yet.

3.) put solution in an ice bath and once it cools

4.) add 1ml of 1 N NaOH and 20ml h2o; stir, stir stir (stuff should start precipitatin')

5.) filter! this should be your cyclizine base!

6.) isolate cyclizine base from anything else that may have been in the solution... (also wash it with h2o a couple times) or maybe admixture's a better word.

7.) either way, add dilute lactic acid to the dried cyclizine base and it should dissolve right before your eyes as cyclizine lactate!

Now i am very aware how hyphothetical and flawed this whole procedure happens to be but it is not only based off of that one source... i have a few more... oh and in case you were wondering here are the inactives:

anhydrous lactose, hydrogenated vegetable oil, magnesium stearate, powdered cellulose, pregelatinized starch, silicon dioxide.

I KNOW! ok thats why i posted this HERE because of all the bastards in the world you'd be the most likely help me (while laughing at me but its all good bring it on)

 

[sekio]

The guys at Opiophile have derived a way to get Cyclizine HCl out of the pills, but not convert it to the lactate... looks like a hot water extraction followed with an acetone wash.

I wouldn't be using methanol for anything you'd (eventually) ingest, it's not a very "neuro-friendly" solvent, and if hot water can do the job instead I would rather use that.

It sounds like you have the right idea though, an acid-base process is exactly what you'd be looking at.

Just make sure to get the pH right. (I assume this is for IV usage.)

 

[CretiNation]

yeah see i looked into acetone and, as if finding info for cyclizine hydrochloride isn't tough enough, acetone wasn't anywhere to be found on any solubility lists. here's one:

http://www.pharmacopeia.cn/v29240/usp29nf24s0_alpha-2-12.html

"Slightly soluble in H2O and alcohol; sparingly soluble in chloroform; insoluble in ether

then this really cool link pops up:

http://www.newdruginfo.com/pharmaco...ical substances\C\Cyclizine Hydrochloride.htm

Prepare the solutions immediately before use.

Test solution (a)

Dissolve 0.20 g of the substance to be examined in methanol R and dilute to 10 ml with the same solvent.

Dissolve 0.5 g in a mixture of 40 volumes of alcohol R and 60 volumes of carbon dioxide-free water R and dilute to 25 ml with the same mixture of solvents. The pH of the solution is 4.5 to 5.5.

D. Dissolve 0.5 g in 10 ml of alcohol (60 per cent V/V) R using heat, if necessary. Cool in iced water. Add 1 ml of dilute sodium hydroxide solution R and 10 ml of water R. Filter, wash the precipitate with water R and dry it at 60C at a pressure not exceeding 0.7 kPa for 2 h. The melting point (2.2.14) is 105C to 108C.

along with my first post it would indicate that methanol is not only preferred but, one could argue, ideal for the dissolution of cyclizine hcl. and what's with the aversion to methanol, sekio??? it's one of my favorite solvents!

ANYBODY WHO MAY POSSIBLY IN ANY WAY SHAPE OR FORM INJEST ANY SOLVENTS USED IN THIS PROCESS SHOULD ABSOLUTELY UNDER NO CIRCUMSTANCES ATTEMPT SUCH A TEK!

yeah i figure if i end up with a ph >4.1 i will have succeeded! thanks for the input sekio much appreciated!

 

[sekio]

Ingest. And methanol, unlike essentialy every other alcohol used as a solvent, tends to cause optic nerve damage and is notably more toxic than... almost every other alcohol.

Another, faster, option would be cold crystallization of cyclizine HCl then reconstitution with sodium lactate solution & boiling. Less fucking around with freebases and I assume you'd make only NaCl as a byproduct.

 

[CretiNation]

hehehe rare does a spelling error play me the fool... you could almost say i made a... rarror... hehehehee *giggle* um anyway does this methanol-caused damage mean anything if the solvent is completely evaporated? i am certain i'd never deal with what isn't.

do you have a link you could refer me to? or if ya feel ya have the time and will to explain how that right there works i'd be a grateful guy. of course i'm just bein' lazy i could just look it up but i'm baked and goin to sleep thanks sekio!

 

[alkap555]

After liberating cyclizine base, why not extract with DCM or Et2O (etc) as an extra purification step b4 formation of the lactate salt? Rinse the organic layer with sat. bicarb, dry with mag sulfate and strip to dryness. Should yield relatively pure cyclizine base, which you can then convert to the lactate.

Regarding the MeOH: As long as you evap it thoroughly. I doubt the amount of residual MeOH would pose any significant health risks. But I like to dessicate rxn products overnight by pumping down in a vacuum chamber.

As for methanol toxicity, it is converted to formaldehyde and formic acid by hepatic enzymes alcohol dehydrogenase and aldehyde dehydrogenase, respectively (same metabolic pathway for ethanol, not surprisingly).

IIRC, formic acid inhibits complex IV of the mitochondrial electron transport chain, thereby disrupting the reduction of molecular oxygen into water and the subsequent formation of the proton (H+) gradient which in turn drives phosphorylation of ADP-->ATP via ATP synthase. In short, ATP synthesis largely grinds to a halt and a form of hypoxic cell death quickly ensues. Overall its mechanism of toxicity is near identical to that of cyanide.

I wouldn't worry too much about residual MeOH as long as you really let that powder dry for a good long while. If you have access to a hard vacuum it wouldn't hurt to pump it down overnight either. My $0.02

 

[CretiNation]

wow alkap that was awesome thank you so much i'm seriously considering this now but to tell you the truth i decided to just go american and 0.22 micron wheel the resultant cyclizine lactate xmg/ml solution :D

but methyl alc and i... well keep it sahara-style. i really do appreciate you puttin' that out there though... didn't even think to self-pity wah. so ok whether y'all keep on bringin' in the knowledge i'll do my best to post my data...