Benzo Liquid Formulation Discussion

[[Af...]]

Thanks for the feedback and instructions. I'll need to read a few times and see if it sinks in. This stuff is so unfamiliar to me and it takes a while to sink in and foggy brain doesn't help. I'm sure that I'll have more questions/explanations.

[[sl...]]

UPDATE!

 

If you've been following my exploration into clonazepam suspensions... sadly my pharmacy compounded pure MCT oil and clonazepam powder suspension was a dud. Suspended fine, dosed easy, stored well... but felt like nothing. By day 6 I was feeling a good-old cut-and-hold, despite my liquid DMT dose that was supposed to cushion the 1/4 pill drop. And that quarter was a 7.7% reduction, so it was a little higher than my past cuts, and I suffered some severe anxiety and instability as a result. I was so confused; I was still taking 50% of that 1/4 pill in liquid form, but I wasn't feeling it. My theory is that the fat content, the MCT oil, dramatically reduces the absorption of the clonazepam for me; I always take my doses apart from food so it threw me for a loop I guess.

 

I made a homebrew ethanol batch to test my theory. 10ml 180 proof organic grape alcohol, ground into 3.75mg of tablets in a mortar and pestle for a good while, then diluted with water in a graduated cylinder to 30ml, for a 0.125mg/ml intended potency. Loaded it in a medicine bottle with syringe adapter, and off to the races.

 

First day on this new liquid I was feeling a huge improvement in symptoms; I had been holding two days with the MCT oil liquid but that wasn't doing jack. On the ethanol brew I drove all over the place, and then RAN 1.25 miles in the afternoon. That was absurd, I'm not a runner, and I'm still recovering from that, but that's how much of a shift took place when I finally GOT a 25% dose of that missing 1/4 pill.

 

I've since tapered to 7% of that 1/4 pill decently (still stabilizing from that hard cut experience with the MCT oil placebo ), and I'll be done with that 1/4 pill reduction tomorrow.

 

So live and learn; you can make an MCT oil suspension, but if you're like me and you NEVER take your medicine with food, it will likely NOT help you micro-taper unless you can somehow transition to ONLY taking the MCT oil suspension, and I have no idea what kind of cut that would feel like making the switch from tablets to oil-based liquid.

 

Sorry! Trial and error. I hope my mistake is your saved suffering. 

[[ki...]]

Figured I might get an answer here to this question... does anyone know if diluting the prescription diazepam solution (Roxane) affects solubility?

[Guest [ba...]]

SlowNSteady - probably don't have to use 10 ml of 180° alcohol.  2-3 ml should suffice.  10 ml 180° is basically a 1 oz shot of 80° alcohol, and most people don't want to drink that much alcohol.

 

Kitsune - it's my understanding that those liquid formulations can be diluted if the dose is taken soon thereafter.  I don't know how long a diluted solution would be stable.  Might be fine for a couple of days??

[[ki...]]

SlowNSteady - probably don't have to use 10 ml of 180° alcohol.  2-3 ml should suffice.  10 ml 180° is basically a 1 oz shot of 80° alcohol, and most people don't want to drink that much alcohol.

 

Kitsune - it's my understanding that those liquid formulations can be diluted if the dose is taken soon thereafter.  I don't know how long a diluted solution would be stable.  Might be fine for a couple of days??

 

Thanks! I was hoping you’d reply. I’ve been making 10 days worth at a time, I’m guessing I should stop doing that. 😆

[Guest [ba...]]

SlowNSteady - probably don't have to use 10 ml of 180° alcohol.  2-3 ml should suffice.  10 ml 180° is basically a 1 oz shot of 80° alcohol, and most people don't want to drink that much alcohol.

 

Kitsune - it's my understanding that those liquid formulations can be diluted if the dose is taken soon thereafter.  I don't know how long a diluted solution would be stable.  Might be fine for a couple of days??

 

Thanks! I was hoping you’d reply. I’ve been making 10 days worth at a time, I’m guessing I should stop doing that. 😆

 

If it's been working then don't change what you're doing.  We just don't have any hard evidence that a solution is stable for 10 days.  We don't even have hard evidence that these solutions are fully stable for two days, although a lot of people make solutions for two days.

[[sl...]]

Yeah kitsune556, I'm with Badsocref on this one; make your life easy and keep doing what you're doing. A dilution for 10 days, in the fridge, shaken before dosing... seems reasonable. It's just got to be working!

 

I might have confused you Badsocref with my recipe. I use 10ml of 180 proof alcohol for 3.75mg of K; that's just a tad over what Ultra2007 swears by (2.5ml/mg of K). Then I diluted to 30ml, so it's roughly 25% alcohol. This is a 50-60 day supply for me. I dose liquid once a day, never more than 1ml. It's not a shot by any means. Am I making more sense now?

[[ki...]]

Slownsteady, I don’t refrigerate or shake as I use the manufactured liquid as opposed to pills+alcohol+water. I’d been told it’s not necessary for the prescription liquid.

[Guest [ba...]]

Yeah kitsune556, I'm with Badsocref on this one; make your life easy and keep doing what you're doing. A dilution for 10 days, in the fridge, shaken before dosing... seems reasonable. It's just got to be working!

 

I might have confused you Badsocref with my recipe. I use 10ml of 180 proof alcohol for 3.75mg of K; that's just a tad over what Ultra2007 swears by (2.5ml/mg of K). Then I diluted to 30ml, so it's roughly 25% alcohol. This is a 50-60 day supply for me. I dose liquid once a day, never more than 1ml. It's not a shot by any means. Am I making more sense now?

 

Yes, that makes more sense.  I thought you were doing shots with your doses.  Not a good idea for 99% of people.  1 ml per day is fine.

[[sl...]]

Slownsteady, I don’t refrigerate or shake as I use the manufactured liquid as opposed to pills+alcohol+water. I’d been told it’s not necessary for the prescription liquid.

 

Of course it's up to you. My pharmacist recommends refrigeration for all her compounded liquid formulas; the cold improves suspension (via viscosity) for most and increases shelf-life for all. Shaking creates a temporary suspension which can go a long way towards making sure each dose is even; manufactured liquid formulas do have a settling rate. So if it's easy, I really recommend refrigerating your liquid medicine (unless it gets too thick to dose), and shaking before dosing (unless it's foaming up too much).

 

Whatever is working for you sounds good. The only issues I see with your approach is you might get uneven dosing across your timeline of using the bottle (higher or lower doses first depending if you pour from the top or draw from the bottom), and this might cause some surprise WD symptoms as you start a new bottle. Again, theoretical, but I don't trust pharmacists to know all, and refrigeration and shaking are easy for me.

 

Badsocref! Glad we're on the same page. Highest dose is 1ml, then it drops daily from there until the 1/4 pill equivalent dose is gone. I'm leery of any ethanol in my system, but after two failed DMTs, I'm going with what's worked for other people. With today's lil' cut I'm back to just tablets, and I'm holding as I rotate my doses around, 30 minutes at a time, to new positions in the day.

[[ki...]]

Slownsteady, I am using the Roxane oral solution though, not a compounded suspension. So that’s why I don’t shake my preparation. I know if it were a suspension then it should be shaken. My understanding is that a solution does not need to be shaken before drawing because all the medication is evenly distributed throughout the liquid. That’s why I initially asked if when diluting a solution it is a true solution or does the medication fall out of solution. I was curious to see if anyone knew for certain, which it sounds like no one does.

[[sl...]]

I understand what you're saying kitsune556. I'm not sure if it's a true solution of all ingredients or if some of them are in suspension. Likely they got it all into solution, especially if they're not bothering to encourage you to shake it. But when you dilute it you're messing with their ingredient ratios, so I would definitely refrigerate your diluted portion, and shake it immediately before dosing. This stuff is a lot like baking; if the ratio isn't right, chemicals behave differently and the results can vary dramatically. Again, I'd err on the side of caution; but of course, don't panic! 

[[sl...]]

Can anyone check my mole to mg chemistry math?

 

Regarding my recent homebrew liquid formula, Libertas sent me this link: https://digital.library.unt.edu/ark:/67531/metadc674044/m2/1/high_res_d/Acree%20Pub-479.pdf

 

I recently made a homebrew with 33.33% 180 proof alcohol, which is 30% ethanol by volume. According to the chart in the study above, clonazepam dissolved at 0.00063 mol/L in 30% ethanol by volume. I multiplied this number by the molecular weight of clonazepam (315.711 https://webbook.nist.gov/cgi/cbook.cgi?ID=C1622613&Mask=200) and got that the study was saying 198mg/L were dissolved in this 30% ethanol mixture.

 

My mixture was only 30ml, at 30% ethanol, which if my math is correct, according to the study can dissolve 5.94mg of clonazepam. I happened to try to dissolve 3.75mg in my formula, so it looks like I may have been successful (barring some ethanol interaction with the tablet binders or the other).

 

Any of this making sense? I'm a kitchen chemist, but I don't want to ignore the data if my solution isn't going to be effective.

 

Thanks!

[Guest [ba...]]

If you use their methods (including sonication), you should expect to achieve their results.

[[sl...]]

Oh yeah, I sang at it, often at high volumes. So, we're good then! Thanks.

[[ki...]]

Oh yeah, I sang at it, often at high volumes. So, we're good then! Thanks.

 

:laugh: What did you sing? 

[[sl...]]

I sonicated with mostly made up songs this time; I can never remember the words. Next time, I'm thinking I might use the guitar as well, since I intend to do a longer ethanol soak for good measure.

 

The study I read was based on 48 hours of soaking in solution, but that was for a 30% ethanol dilution right from the start; I'm working with 90% and then watering it down. To my mind, a higher ethanol concentration from the start should dissolve faster; I can't be sure of that though, hence the possible addition of stringed instruments and a longer soak/stir time. I could drag out my shiny magnetic stirring hot plate and just leave it on stir mode for a few hours... Feels like overkill though.

 

My compounding pharmacist, I can't remember if I mentioned this, she said she's going to try to make me up a new batch with 200 proof ethanol and water. I sent her the study Libertas sent me, and as Libertas was suggesting, she plans to test it for precipitating during the dilution by going very slowly when diluting and adding more ethanol if clouding occurs. She also consulted with her "clinical team", I have no idea what that means, but they agreed this type of stable solution should be possible with ethanol and water. Her initial expectation was that 30% ethanol would be necessary for the 0.125mg/ml that I'm requesting. Funny though, neither her nor the clinical team could find the study Libertas sent me until I emailed it to her. It takes a village...

[Guest [...]]

My compounding pharmacy did this first for me.

They had consulted with a bunch of colleagues in the States.

 

Unfortunately, I reacted to the alcohol!

 

 

[[sl...]]

WinnieDog, did you say previously or on another thread that you do tolerate a PG solution? But not the ethanol? What was the clue for you that you were reacting to the ethanol?

 

Thanks!

[Guest [...]]

A immediate excruciating headache.

 

I haven't been able to have any alcohol, since I took antibiotics last spring.

The antibiotics did something to me, was immediately filled with crazy physiological anxiety, increased heart rate out of nowhere.

I appear to now not be able to have any sugar since that point either, which is probably why the alcohol gives me the headaches, so does pasta, peanut butter, lots of carbs etc.

 

It was the antibiotics which led to the ativan - my heart kept going to 180 and staying there for hours.

 

I seem to be ok with the PG, but the liquid is just not working for me at all, it's like I'm not getting a dose.

So I'm in the process of trying to crossover to Valium

 

 

[[sl...]]

I'm so sorry to hear that WinnieDog. This is an aside, but I hope you will do a gradual crossover to Valium; so many people recently are being switched suddenly to and from V, and not doing well after either change. You probably know already, the Ashton method for crossover to V is a month or so, and this is based on a number of pharmacological reasons.

 

I already have plenty of headaches; I didn't notice any new ones taking the ethanol homebrew, but I also do a hybrid liquid/tablet taper which minimizes my liquid intake. My once-daily liquid dose is always less than 1ml and usually much smaller, so at 30% ethanol I'm still only getting tiny amounts of alcohol.

 

I am wishing you the best WinnieDog! Thanks for replying.

[Guest [ba...]]

Bath sonicator frequency will be somewhere around 30,000 Hz.  To get the same energy from your guitar, you'll need a big amplifier since guitar feedback is usually only 100-400 Hz.

 

[Guest [ba...]]

I did a little kitchen science today to explore converting tablets into liquids.

 

I used a common histological dye (Sudan IV) for the experiment.  It has a bright red color that's very easy to see, and it has solubility parameters that are similar to many benzos.  It is insoluble in water and only slightly soluble in alcohol (1 mg per ml - roughly similar to klonopin).  It's also sparingly soluble in acetone (again similar to klonopin).

 

Experiment 1 - Dispersion of Dye Directly Into Water Versus Using Alcohol to Initially Solubilize the Dye.  I added c. 1 mg of dye to 45 ml of water in a 50 ml plastic tube.  The dye just sat on top.  I shook it well for 5 minutes.  The dye did not disperse noticeably.  Upon sitting, the dye particles quickly floated back to the top of the water.

 

http://enchantedskies.net/KlonOnWater.jpg

 

I also tried first dissolving some dye in a small amount (c. 1 ml) of 95% ethanol before adding the water (to 45 ml).  The dye dispersed (dissolved) into the ethanol within seconds.  Water was then added to give 45 ml.  The dye remained evenly dispersed in the solution.

 

http://enchantedskies.net/DyeInEtOH2.jpg

 

Experiment 2 - Dispersion of a 'Pill' Directly Into Water Versus Using Alcohol First.  I formulated a couple of 'pills' using either the dye and either cornstarch or sugar as a filler.  In each case I added c. 1 mg of dye to c. 200 mg of filler then crushed thoroughly using a mortar/pestle.

 

I placed each (crushed) 'pill' into a tube and added 45 ml water.  The dye dispersed surprisingly well in both cases.  The starch-containing sample was turbid as expected.  The sugar-containing sample was uniformly red and water clear.  A few flecks of un-dispersed dye was floating in both samples, but 90+ percent appeared to be well dispersed.  The starch-containing sample slowly settled out with the dye settling out seemingly in association with the starch.  It could be easily re-dispersed with a little shaking.  The sugar-containing sample remained visually dispersed for an hour (then I got bored and tossed it).

 

I also placed a 'pill' into a little alcohol first (before adding water).  Since most folks don't have 95% ethanol sitting around, I used tequila (I didn't have any vodka laying around, but it would work just the same).  I added c. 2 ml tequila to the 'pills', swirled them around for around 15 seconds, then added water to 45 ml.  The results were very similar to the water-only trial (above); however, no insoluble flecks were apparent.  The starch 'pill' sample again slowly settled with the dye appearing to be associated with the settling starch.  The sugar 'pill sample was again water clear.

 

http://enchantedskies.net/DyePills.jpg

From left to right: Ingredients, dispersion of starch pill in water, settled starch (and dye) about 45 minutes after mixing, dispersion of sugar pill in water.

 

My Conclusions.  The dispersion of the dye in regular water worked surprisingly well although there were a few small flecks of un-dispersed dye floating atop the water.  Perhaps using a pill with micronized ingredients would disperse completely???  Dispersing the pill in a couple ml of alcohol worked better in that there were no apparent insoluble flecks of dye.  I think the pill needs to be thoroughly crushed (mortar/pestle) prior to trying to liquify it.  Since there is some loss in the mortar/pestle, the powder will need to be weighed before liquifying it.  Since starch is the more common filler, the suspension will likely need to be agitated immediately before measuring/consumption.

 

Questions/comments are welcome.  If you can think of another experiment that should be done, let me know.

[[sl...]]

Hey Badsocref! Thanks for sharing your experiment. It seems a very clever way to visualize the dissolution (or lack there of) of a medicine like clonazepam. I can't confirm whether this dye you're using is analogous to the medicine as you say, but if it is, I'm wondering what your thoughts would be about the recipe I wrote (link in my signature).

 

My pharmacist did a somewhat similar experiment with powdered clonazepam; but since my order is worth $30, she wasn't doing a variety of trials. After reviewing the medical study Libertas gifted me, and speaking with her "clinical team" she decided it would work to do an ethanol and water solution. She added ethanol slowly from a pipette into the powdered clonazepam until it was fully dissolved and then some, then added water to the prescribed dilution, and then let it sit on the counter over night to make sure it didn't precipitate out. She went a little heavy on the ethanol (30%) based on the medical study suggesting this range was necessary for the mg/ml I was prescribed; she was in a hurry, I suspect because she wasn't getting paid much for her trouble.

 

Since my pharmacist started with 200 proof alcohol, and went heavy on it (based on the study results), I suspect this is why she got quick and stable results. The medical study that used a similar dilution did not appear to start with pure ethanol; instead they used the final dilution, and gave the mixture 48 hours to dissolve.

 

So my remaining question is, how much longer does it take to dissolve clonazepam tablets if the alcohol used is, say, 80 proof? It looks like your experiments suggest it wouldn't be 48 hours, but I'd like to see this experiment of yours repeated with clonazepam powder; I think failed dissolution or precipitation would be fairly obvious by the occurrence of sediment or clouding.

 

Should I request powdered clonazepam from my compounding pharmacist to do my own trials? I'm not sure how my doctor would feel about purely academic prescriptions... 

[Guest [ba...]]

I chose the dye approach since I don't have a readily-available HPLC/UPLC sitting around anymore that I could use to detect/quantify klonopin.  I also don't have any klonopin laying around.  It's an easy experiment to do if you have these things.  The LC detection method is published.  Just need a photodiode array (PDA) detector on the HPLC to 'see' the klonopin.

 

My final alcohol content was 2% by volume.  Maybe I'll go whip up another batch and stick it in the fridge for a couple of days to see how it looks.  30% seems like overkill to me, but it may be better for storage??