Clonazepam in Solution (Ethanol + water) questions

Hello BBs,

 

I could use some help with creating a multi-dose "solution" for Klonopin using ethanol and water. I have some preliminary reductions to make in order to even up my doses. The first step will require reducing 0.25 mg of clonazepam from one of my 3 doses.

 

Currently, I am placing 0.5 mg of clonazepam in 100 ml of water (0.005 mg/ml concentration) and reducing by 1 ml every day and have made a reduction of a total of 13 ml's. It's a start to a very long process. I don't like using water because I have zero confidence that I am getting even close to accurate reductions due to the very low insolubility of clonazepam in water.

 

When I was last on BB which was quite some time ago, using ethanol + water according to Jouyban-Acree Model was becoming a popular yet controversial subject concerning creating a "true" solution vs. the uncertainties of using water in an attempt to suspend the drug. If I am not mistaken, Jouyban's Table of Solubility suggested that it took about 1 ml of 80 proof ethanol to dissolve up to 0.6 mg of clonazepam.

 

My understanding is that I would need to use 25 ml's of 80 proof ethanol, add 7.5 tabs of clonazepam, allow them to turn into a slurry, stir, and add water with a pipette to the 30 ml line on the glass cylinder to make a 0.125 mg/ml concentration. What is the percentage of alcohol contained in 30 ml's of the homebrewed solution?  This is a pretty hefty concentration equivalent to 2.5 mg of diazepam.  How can I make a 0.1 mg/ml concentration using 0.5 mg tabs? My concern is minimizing the amount of ethanol needed.  Perhaps I should not be too concerned over this because I did fine with Roxanne's diazepam solution and I believe that contains 19% alcohol.

 

Here is my taper plan from http://benzo.alwaysdata.net/ https://drive.google.com/file/d/1MO5xEYDZSsLNVOplG-k6DJ5CXpk4hS2o/view?usp=sharing.

Would I start at day 25 or am I reading this incorrectly? 

 

Thank you for reading and any suggestions.  Aja

 

Edit: Located info re syringes and added discussion of concerns re amount of alcohol.

 

Hi Aja56,

Welcome to the forum. A couple thoughts of mine...

 

25ml of 80 proof is 10ml ethanol. Diluted to 30ml = 30% ethanol. 30% ethanol was shown to dissolve a maximum of 0.2mg/ml of pure clonazepam. I think this is sufficient for 0.125mg/ml of clonazepam from tablets and it's been very effective in my use, although I always treat liquids made from tablets as suspensions for increased reliability.

 

To my understanding, Jouyban's info on solubility of pure clonazepam in ethanol-to-water ratios does not directly correlate to clonazepam from tablets, or mixtures made without 48 hours of agitation at a steady temperature and a fixed concentration of ethanol. Adding 1ml of 80 proof to a 0.5mg tablet of clonazepam and even waiting and stirring for an hour, then diluting to 100ml, has changed so many variables from Jouyban's results it's impossible to compare what has occurred with regards to dissolution. Personally I suspect the results of such an at-home deconstruction of tablets is almost entirely a water suspension.

 

The reason I make a 0.125mg/ml liquid K from tablets is because I do a liquid/tablet hybrid with 0.5mg tablets. This means I'm only ever taking 1/4 tablet worth of liquid per day, so 0.125mg or less, measured as 1ml or less, which is also 0.3ml of ethanol or less. The rest of my dose(s) I take as dry split tablets, which I can accurately split into 1/4s using my aluminum pill splitter. 0.1mg/ml is less convenient for liquid dosing with this approach because the start of every liquid reduction would be more than 1ml of liquid, and I'm using a 1ml syringe with 100 gradations.

 

I'm glad to see that you can use the DMT schedule generator. You might want to consider exploring a few features, specifically the percent-based reduction option, and the 'Combine with Tablets' option.

 

Percent-based reduction rates may be more symptomatically consistent, although they make the taper longer. At low enough doses a linear taper might make more sense but at doses above 0.125mg K I consider percent-based more reliable.

 

The 'Combine with Tablets' feature will create a liquid/tablet hybrid schedule. The generator assumes the tablets you listed in the Medication section are what you have on hand, and that you can divide them reliably into 1/4s.

 

Regarding where to start on the taper schedule you made, I suggest just making a new one and using your actual dosages in milligrams in the Daily Dose(s) section. From what you describe it sounds like with your 13% reduction of a 0.5mg tablet, you are dosing 0.435mg/day.

 

I'm not sure what you mean about a "hefty concentration equivalent to 2.5 mg of diazepam".

I hope this helps. 

Hi Slownsteady,

 

Thank you for your reply.

 

Yes, I agree with you entirely that it is a mistaken belief to try and use the Jouyban-Acree model using tablets vs. pure clonazepam powder under non-laboratory conditions expecting to be able to emulate a pure solution.

 

I'm not sure what you mean about a "hefty concentration equivalent to 2.5 mg of diazepam".

 

The concentration of my "suspension" is (very roughly) 0.005 mg/ml (0.5 mg in 100 ml) and I am not pill-splitting. I feel uncomfortable with pill-splitting anything other than diazepam due to my body's unique physiological relationship and sensitivities toward clonazepam. That is why I characterized your suspension/solution as being "hefty" or highly concentrated (for me) at a V-equivalent of 2.5 mg/ml.

 

What are some options that you might try if you chose not to pill-split, were working with full 0.5 mg tablets of clonazepam and wanted to reduce one of your daily doses of clonazepam by 0.25 mg over time using ethanol + water?

 

I thank you for your time and dedication to the community.  Aja

 

I understand what you mean now, thanks for clarifying!

 

It might seem "hefty" but with a 1ml syringe with 100 gradation, I can reduce by 0.00125mg intervals; this is more than sufficient for my current daily reductions (DMT) at around 0.4%/day. However, at daily doses below 0.125mg I don't want to be using 0.125mg/ml of liquid clonazepam for my liquid/tablet hybrid DMT; the accuracy just doesn't seem high enough, so I'd need a more dilute formula. Maybe I'd switch to all liquid at that point and do a daily linear reduction schedule; so far in my taper I haven't gotten to that problem yet!

 

I understand your goal is to avoid tablet splitting; it's my opinion that splitting scored tablets into 1/4s is "reliable enough", but my goal isn't to change your mind. I think that in a big way, how we dose and how we taper is personal preference.

 

What are some options that you might try if you chose not to pill-split, were working with full 0.5 mg tablets of clonazepam and wanted to reduce one of your daily doses of clonazepam by 0.25 mg over time using ethanol + water?

 

The answer to this question would be based on how often I wanted to reduce. I like to taper DMT, using the generator you're familiar with, so I'm going to think about this for a DMT which requires a suggested reduction amount in the 0.3-0.7% range. To make this easier I'll use the avg at 0.5%/day. At 0.435mg/day that starts with needing daily reductions in the 0.002mg range, and at 0.25mg/day daily reductions need to be in the 0.00125mg range. So I would consider using the lower of these two to get to 0.25mg with a DMT.

 

0.00125mg happens to be the degree of accuracy with which 0.125mg/ml can be reduced using a 1ml oral syringe with 100 gradations. So that's the concentration I'd be looking to make my liquid to get from 0.435mg/day to 0.25mg/day with reductions at 0.5%/day.

 

To make 0.125mg/ml from 0.5mg tablets without splitting a tablet, I'd need to make a batch size in intervals of 20ml, each made from 5x 0.5mg tablets (2.5mg total). This could be scaled up to any interval of 20ml with (total ml)/20ml * 5 = (tablets needed). Ex. 60ml/20ml * 5 = 15 tablets.

 

I'd be needing to consume more liquid since I wouldn't be using dry tablet pieces. I would need to dose with two syringe sizes, one that holds 10ml and one that is 1ml with 100 gradations. The first syringe would be for taking out whole milliliter doses and the second would be for taking the decimal place. Ex. 3.48ml is 3ml with the 10ml syringe and 0.48ml with the 1ml syringe.

 

To make a 0.125mg/ml solution/suspension with a solvent from tablets, I'd want 30% ethanol. At 0.435mg/day I'd be dosing 3.48ml of liquid per day which is 1.04ml of ethanol per day to start and declining with each reduction; for comparison a single shot of 80 proof vodka is ~17ml of pure ethanol. So it's more ethanol than I'm consuming with my liquid/tablet hybrid, but it is still a very small amount of ethanol.

 

As for how much alcohol I'd to use for to make 20ml at 30% ethanol or any other batch sizes...

 

1. (final volume of solution) * (decimal percent of ethanol desired) = (ethanol required)

ex. 20ml * 0.3 (i.e. 30%) = 6ml

 

2. (ethanol required) / (decimal percent of ethanol in alcohol) = (alcohol required)

ex. 6ml / 0.4 (i.e 40% for 80 proof vodka) = 15ml

 

To be fully transparent, these are just my initial thoughts on the matter. Life constantly proves to be more complicated and surprising; I like to joke that no plan survives first contact with biology. But regardless, if I was tapering from 0.435mg to 0.25mg beginning tomorrow, these are the thoughts that I would be starting with.

 

I hope this helps. 

Hello,

I thought I had the 30% ethanol concentration pretty well understood until I read this document....https://benzo.alwaysdata.net/titration/titrationHelp.htm?help=Readme+First.  This document, which I believe I found on this site seems to suggest that 2ml of 80 proof vodka per 1 mg of clonazepam is all you need and the amount of solution prepared is irrelevant.  In fact it goes on to say that 1mg of K, plus 2ml of vodka, plus 98 ml of water is all you need for 100 ml of a 0.01 concentration.  That is a near infinitesimal % of ethanol.  So is ethanol % a function of milligrams of medication or volume of solution or a combination of both?  Thanks

So is ethanol % a function of milligrams of medication or volume of solution or a combination of both?

 

Great question! There recently was a buddy on here, Builder, who professed that 2ml of vodka could dissolve 1ml of ANY benzo, and then be diluted to ANY degree with water. I think he gave this advice to many buddies, but eventually he got called out on it and talked himself in circles, eventually leaving the forum to-date. Here is the final thread he was on; this link will take you to where I think it gets interesting...

http://www.benzobuddies.org/forum/index.php?topic=235642.msg3025689#msg3025689

 

I think Builder was imagining that once a benzo was dissolved, assuming a benzo was dissolve, it would stay dissolved forever. In my limited experience and research, this isn't how solutes actually behave.

 

Just in the simplest sense, I believe that precipitation of the solute can occur when the solvent is diluted past a certain point. To guess where that point is with a benzo in an ethanol and water mixture, I think we only have the Jouyban's data (and maybe a few other sources), which in Builders own words, chiefly demonstrate that "solubility varies with the alcohol:water ratio". By this apt point, if we dilute that ratio later with more water we've left the intended ethanol:water ratio that we were originally using (40% in the case of Builder's suggestion) and now have a different and potentially much much lower ratio. And from the data we do know that a lower ethanol:water ratio holds less of the benzodiazepines that Jouyban studied.

 

So my interpretation is that there are two basic false assumptions in the approach that Jim Hawk describes in his Read Me notes. 1) That a solute in solution will stay in solution even if the primary solvent is radically diluted and 2) that ALL benzos dissolve significantly in casual, hurried attempts at dissolution from a tablet form with relatively dilute forms of ethanol.

 

I do not think we have any research data that supports these two assumptions; instead I think we actually have data that contradicts the first just from basic chemistry, and we lack the data to assume the second, even in the case of the few benzos that Jouyban published data on, because they were using the pure active drug substance, not tablets, and waiting 48 hours (I believe under constant agitation at a fix temperature, but I'm forgetting all the details...).

 

So it appears to me that Builder was make huge and potentially erroneous assumptions, and yet people were (and likely still are) using this method to confidently taper their benzos! I joke that the 1:2:8 method is a water suspension from tablets, with a bit of alcohol for taste.

 

Water suspensions work. I think they have great benefit in their simplicity. But since we're dealing with critical-dose drugs and we're speaking to a population of people for whom the rapid doctor-led tapers generally haven't worked, I think leaning towards more accuracy than less is prudent. Water suspensions, IMO, lack the accuracy that I believe can be obtained by other methods.

 

That being said, I think a number of tricks can potentially increase the accuracy and reliability of a water suspension, and one of these could be doing a solvent-and-tablet "wetting phase" which is what Builder was describing, but I strongly suggest NOT treating the resulting mixture as a benzo solution. Such a hurried mixture and radical dilution of the primary solvent is still, in my opinion, a water suspension and requires careful handling for being such an unstable suspension.

 

Just to be very clear, I have nothing against doing a water suspension. I have everything against making false assumptions and gross generalizations in tapering procedure on a forum of members that generally need extra care and reliability in their use of critical-dose drugs. For those that taper with the 1:2:8 method and are comfortable doing it, I support them in their choice of taper method. My findings indicate that there's just not evidence to support the claim that this method produces a true solution of all benzos.

 

I hope this helps. 

builder was the one that helped me and said 2ml of vodka per 1mg of Xanax (or klonopin) -- dissolves quickly and then add in your water, shake vigorously and take out your 1ml or 2ml, toss that out, and you've got your solution

builder was the one that helped me and said 2ml of vodka per 1mg of Xanax (or klonopin) -- dissolves quickly and then add in your water, shake vigorously and take out your 1ml or 2ml, toss that out, and you've got your solution

 

Hi 300days!

What you're describing making is highly unlikely to be a "solution".

 

Builder did not supply evidence to support the quoted claim (in bold). I have not seen any research data about the dissolution of alprazolam in ethanol and water mixtures. Furthermore I have not seen any research data that supports the quick dissolution of ANY benzo in 40% ethanol mixtures; Jouyban's data, again, was based on using the pure chemical form of the few benzos they tested, and 48 hours of continuous agitation in an incubator.

 

A point of confusion that I've run into on the forum is buddies not understanding that there is a HUGE difference between the deconstruction of a tablet and the dissolution of it's medicine content. I've often heard buddies claim they can see the medicine in tablets dissolve quickly or completely; this is not the dissolution of the medicine. With all the filler in tablets, we cannot visually verify that the medicine has dissolved, only that the tablet has deconstructed.

 

I've also noticed a point of confusion on the forum about what makes a solution. To my understanding, a solution (sometimes emphasized as a "true solution") specifically consists of something (a solute) being fully dissolved into a solvent. In the simplest terms, to be dissolved the medicine has to change from a solid to a liquid.

 

With the few benzos that have been studied for dissolution in ethanol and water mixtures, we know that this dissolution is limited and also proportional to the ratio of ethanol to water. Diluting a solution of a benzodiazepine made with ethanol and water, were one to be successful made, further reduces the ethanol content, reducing the aforementioned ratio, and reducing the chance of the solute staying dissolved. This can result in the solute precipitating out of the solution, returning to it's solid form. The result of a solute remaining in a liquid as solid particles is not a solution; instead this is called a suspension.

 

When a tablet deconstructs, with or without a little ethanol in the mix, and the medicine particles and some excipients float around as they do when using the method Builder describes, the result is primarily a suspension. Medication suspensions have dosing accuracy dependent on their stability.

 

Suspensions have characteristics which determine their stability, two of which are particle size of the medicine and the viscosity of the suspension vehicle. The "shake vigorously" instruction is important because agitation of particles creates the suspended state, but I've found that the particle size of the medicine and viscosity of the suspension vehicle largely determines the window of time that the suspension is stable for dosing. With water and gently deconstructed tablets, this suspension stability seems to be much much lower than what may be necessary for accurately dosing many critical-dose medications like benzos.

 

While the method described by Builder appears to produce a suspension of deconstructed tablets and includes a potentially useful solvent wetting stage, it lacks mention of a number of other ways in which this situation could dramatically be improved. One is reducing the particle size of the tablets to as small as possible, such as all compounding pharmacies do when preparing a suspension of a medicine, by using a mortar and pestle. Another is increasing the viscosity of the water by adding ingredients to this effect (ex. a proprietary suspension vehicle like Ora-Plus, a mucilage containing product like xantan gum or methylcellulose (https://en.wikipedia.org/wiki/Mucilage), vegetable glycerine, or maybe even honey).

 

The risks of dosing a homemade water suspension are nebulous. If you're doing it and your happy, I'm happy! But a suspension of deconstructed tablets is NOT primarily a solution, and I have yet to see ANY evidence that 2ml of vodka quickly dissolves 1mg of alprazolam (or clonazepam for that matter). I believe that Builder said this and thus the impetus isn't on you 300days to provide additional evidence. However, Builder didn't support these claims, and I suggest not using his claims to advise other members.

 

I know your taper has been challenging 300days; have you considered the possibility of the method suggested to you by Builder having contributed to your difficulties?