Benzo Liquid Formulation Discussion

For those wishing to make liquid formulations of benzos, information can be confusing and contradictory.  Let's collect some tried and true recipes for making proper formulations.  If the method if published, please cite the reference (even if it's in a non-scientific forum).  Else, please write out the steps so they can be clearly assessed.

 

Feel free to speculate, but PLEASE DO NOT attempt to make or use any formulation that has not been demonstrated to be safe and efficacious.

 

We have several folks in the forum with decent backgrounds in chemistry, pharmacology.  Perhaps we can learn from each other, avoid dumb mistakes and possibly even advance the science a bit.

 

To get things started - here's a link to a pdf with solubilities of diazepam and klonopin in various combinations of PEG200, PG and water. 

 

https://www.researchgate.net/publication/234107573_Solubility_of_Clonazepam_and_Diazepam_in_Polyethylene_Glycol_200_Propylene_Glycol_N-Methyl_Pyrrolidone_Ethanol_and_Water_at_2982_to_3182_K_and_in_Binary_and_Ternary_Mixtures_of_Polyethylene_Glycol_200/link/5b9aa47a299bf13e602bd5f3/download

Thank you Badsocref for starting this. I respect the research reports that you and others have such access to and fluency in; I for one, can't make sense of most of it, and get almost nothing from the research findings. I'm just a kitchen chemist, with my little graduated cylinders and pipettes, scale, and mortar and pestle.

 

I'd love it if we could put together some proven liquid recipes that folks without a chemistry background can understand and mix at home! I hope that's not a tall order. Thanks in advance!

 

Here's another link to a solubility study.  This one uses water and NMP/water mixtures.

 

https://core.ac.uk/download/pdf/189463677.pdf

 

If I'm reading this and the previous referenced solubility study, there is a pretty large difference in the water-only solubility of both diazepam and klonopin between the two studies.  Both solubility findings were very low, but the molar concentration varied by around 10 fold.  That may point to difficulties in getting these compounds into water-only solutions - even in a laboratory setting.

This seemed like a relevant article.... 

 

https://withdrawal.theinnercompass.org/taper/making-liquid-mixture-using-immediate-release-tablets-or-capsules

Thanks for these links Badsocref! I read the info at Inner Compass and it was a really useful overview of these kinds of decisions (nice breakdown of pros and cons). I was a little surprised when that site doubted the use of ethanol or other solvent in making a liquid solution; they might be right though.

 

Today I'm thinking of using vegetable glycerine as a suspending agent at maybe 80-90% of the solution; that would let me use 10%-20% water to dissolve the tablets (maybe not necessary), then suspend what's non-water soluble in the VG. I'm wondering why I haven't heard of VG being used in this way. It has so many advantages, such as being clear and being food grade and a preservative to some extent. Any ideas? Can't be worse than pure water, which seems to be one of the "tried and true".

Drawing from the cannabis lab days...  VG is a very poor solvent for THC/CBD.  I haven't seen anybody use VG to solubilize/suspend benzo pills.  VG has a high dielectric constant.  Benzos (and cannabinoids) prefer solvents with lower values.

 

Good explanation about pharmaceuticals and polarity considerations here...

 

https://pharmlabs.unc.edu/labs/solubility/structure.htm

Badsocref, I asked about using VG as a suspension agent. You've given me information about using it as a solvent. Am I being unclear or is there a reason that solvency has to be considered when using a suspending agent?

VG is viscous, so like gums it may help keep insolubles dispersed in solution.  But first you've gotta get the drug dispersed.

I hear you. So I was suggesting dissolving the tablets in a little water, then adding VG, then vigorous shaking. Am I skipping a step?

I've come around to VG because a pure MCT oil suspension was proving tricky to make at home. The tablets have to be finely powdered because they didn't seem to dissolve well in the oil, and it was a dusty mess. I'd much rather use a little water to dissolve the tablets and then keep everything in liquid from there on.

 

I purchased some pharmaceutical grade VG from non-gmo palm. I'm going to be doing a negative control, where I take 1ml of the glycerine per day for a couple days to test if I'm tolerant of it. Then I'll feel comfortable using it in liquid formulas. My way of using it would be as only as part of a 1ml or less dose of total liquid medicine per day; I'm just a little paranoid. I know glycerol was in the liquid suspending agent I couldn't tolerate, so I want to eliminate that as a possible cause of my reaction.

 

I chatted up my chemistry buddy, and we came around to imitating the liquid suspending agent my compounding pharmacy had used, minus the "bitter blocker". The most useful ingredients seem to be MCT oil, VG, and water. VG and water alone might do the trick to dissolve and suspend the tablets, but MCT could have it's uses as well. MCT oil is super safe to eat in amounts far beyond a ml (for me anyways), so with VG as an emulsifier, I could get the water-dissolved tablets suspended in the MCT. That way I'm eating more MCT and less VG.

 

If for some crazy reason I can't tolerate VG, liquid sunflower lecithin comes to mind as a substitute for emulsifying water-dissolved tablets into MCT oil.

 

Again, just to clarify, my goal isn't some super-stable suspension of clonazepam. My goal is to suspend dissolved tablets evenly enough for a few minutes to draw a decent little dose as part of my liquid/tablet hybrid DMT; each dose is less than 1ml and I only need 15ml of solution to last a month or so. I honestly think I could get away using plain water, but where's the fun in that? Or the preservatives? 

 

I hope I haven't rustled too many feathers with my kitchen chemistry antics. I also hope I can learn more here and grow this body of knowledge and techniques for other benzo buddies who have sensitive guts.

 

 

I don't know how well you'll solubilize (or disperse) klonopin in water.  It's very poorly water soluble.  That's why I posted the two journal articles - to show people just how difficult it is to get klonopin into water (even in a lab).

Oh, I didn't understand that you were using disperse to mean the same as dissolve (solubilize seems to suggest using a detergent to dissolve a fat, but I might have that wrong). I think that solubility isn't an option with clonazepam, even at a pharmacy, possibly not even with ethanol or other relatively safe solvents (though folks are trying!).

 

With the water titration method, which I've admittedly only studied in passing, people are just shaking water-dissolved tablets in more water. I am planning to do something similar, only instead of diluting with more water, I'll dilute with a slightly more viscous medium with preservative qualities. Basically, dispersal/suspension by shaking; I'm not going for any clonazepam dissolution here.

 

Can't promise I'm using any chemistry terms right... I had to edit this to fix a few.

 

As a side note, I've heard of someone taping their solvent solution (in a jar) to the arm of a scroll saw (the part that vibrates rapidly) and leaving it running for many hours. Just a funny experiment they did to try to improve dissolution, into I think VG or PG, manually. I'm hoping I won't need to go to that extreme for my suspension.

 

The VG and/or MCT oil medium won't be like a gel or anything; the pharmacy mix was rather thin, would partly settle every day and required vigorous shaking before drawing a dose. Seems to me like the industry standard for suspension stability isn't very high; the goal is just that 5 minute window of drawing an even dose.

 

Do you think more agitation is necessary for dispersal than just shaking?

Agitation is certainly important.  Labs use bath sonicators - often for 15-20 minutes - to improve mixing.  They use ultrasonic sound to mix.  The scroll saw thing is more basic agitation, but still helps.

 

The problem with water only is knowing where the drug is.  Is it dispersed in the water or is it sticking to the side of the glass jar?  I recall seeing an Ativan stability study where researchers found the drug tended to stick to plasma bags instead of staying in solution.  A lot of work goes into these drug solubility studies.

Hello. I am going to start a daily micro-taper with holds as necessary. I am waiting until after my next menstrual cycle as that's double jeopardy here for me. 

So I have a few weeks. I'm currently in a nice window-or it could be the drastic diet change-have been juice cleansing for 5 days and able to adhere to it well-mostly green juice, with cashew milk an hour before bed to aid in sleep ( it's working & I do not want to jinx this so that's all I can say    )

I'm going to order what I need and will be tapering from .75 mg Klonopin. I know this is a daily tapering group but I'm taking it very, very slowly from this point forward. I do not have a lot of finances and I have some help from my pharmacist. I cannot use a compounding pharmacy so I'll be making this myself. I'm reading through the material and wanted to get involved, so to say. I was hoping I can use a high raw nut milk like my cashew milk as I see in these posts that water is not the best option.

So hello and any input or 1st step preparation suggestions would be so very appreciated. Blessings!

 

I kind of doubt if regular store brands have enough fat in it to carry the benzo.  Whole milk is around 4% fat.  Apparently, one can make their own cashew milk that has much higher fat content although I don't know the final percentage.  I would think that you'd want to stay near or above the content of whole milk.

Welcome Annie4! Your juice cleanse sounds like it's helping; I drink fresh raw vegetable juice, usually first thing every morning. This isn't a daily micro titration group; and even if it was, you set your own speed! Are you going to emulate the daily water titration method, dissolving your dose and tossing your reduction quantity?

 

I thought the benefit of using full fat milk as a suspension agent was that the milk had been homogenized; in the homogenization process, the fat is put through a machine at very high pressure, breaking the fat molecules down so that they disperse evenly in the milk. I don't know if the fat itself interacts with the benzo, but it does make for a slightly more viscous fluid, and thus a better suspension agent than pure water.

 

Does fat grab to benzo molecules? A question for the experts...

 

I like the creativity of trying cashew milk; to my mind, anything thicker than water, with an even consistency, would be a better suspension agent (short of a gel). Badsocref is right, there's probably not nearly as much fat in cashew milk as whole milk. I tried to look this up but didn't get far, sorry... 

 

Annie4, have you seen liquid/tablet hybrid tapering? You can use liquid for only that 0.125mg (1/4 of a 0.5mg tablet) that you're actively reducing, and then tablet(s) for the rest of your dose. This reduces the impact of your liquid approach. Here's the site I use to do the math for mine: http://benzo.alwaysdata.net/titration/titrationForm.php

 

It's spring-time everyone! Tapering season is upon us. 

Many benzos are fat-soluble.  Benzos seem to like that environment.  I assume they associate with the milk-fat micelles in whole milk.

 

According to a recipe I found, homemade cashew milk should contain close to 12 grams of fat per cut, so 50% more than whole milk.  I think it could work for you.  The store-bought stuff has much of the fat removed and won't work as well.

 

The published solubility of klonopin in water is around 11 mg per liter.  That's just 1.1 mg per 100 ml and it takes a lot of work (sonication) to get that much into solution.  So in theory, the folks using 300 ml of water to suspend a pill might be able to get the drug into solution if they're patient enough and if the klonopin doesn't move to some more desirable matrix (e.g. the glass or plastic container).

 

The idea of first solubilizing in ethanol  (or PG) is to speed up the solubilization.  Ethanol is a much better solvent so the benzo should go into solution much more easily.  Solubility in 80-90% ethanol is around 2000 mg per liter so a few ml should easily solubilize 1-2 mg of klonopin (valium is even more soluble in ethanol).  Then, when water is added, the benzo should disperse pretty evenly.

That's great what you found out Badsocref. I wonder how well those fat molecules disperse in the cashew milk.

 

A quick update, I just got off the phone with my compounding pharmacist. She was very flexible in what she could offer me. She could send me powdered clonazepam suspended in water, but she agreed that VG would be a better suspension. She also thought MCT oil could be useful in the solution as well, in part to reduce the amount of VG I'm eating. She didn't seem terribly concerned about me mixing my own with these ingredients, but she wanted to do some tests to make sure that VG would remain stable mixed in MCT. Since she has a full pharmaceutical lab, hood, mortar and pestle and everything, and she's very affordable, I'm thinking I'll get another batch from her for my next DMT attempt.

 

I'm going to start my negative control with vegetable glycerin today; this is just to make sure it's not some crazy gut irritant or something. I'll probably have the pharmacy compounded mix to start cutting early next week.

 

I may still try mixing my own in the mean time. I still think homebrew with tablets is possible for this kind of VG/MCT type suspension, and I know many folks can't afford or can't access compounding.

My pharmacist did an experiment with 50% VG and 50% MCT, passing it back and forth between two syringes. She didn't find that they incorporated well at that ratio; I'm taking this as a clue for future experimentation, guessing that the VG needs to be a smaller proportion.

 

My pharmacist offered to make a suspension with either pure VG or pure MCT. I placed an order for the pure MCT oil (from coconuts) suspension of pure clonazepam at 0.125mg/ml, and I should have it at the end of the week. I'll report back on how stable this simple suspension is; at least it will be well preserved in the oil.

 

I'm really looking forward to cutting daily again; I'm just not comfortable with my current dose. I feel like an emotional zombie.

I'll be interested to see if a lecithin/oil/water/benzo emulsion will work.  Wouldn't need much oil in the final product - maybe just 10%.

Hi everyone,

There is much talk about Klonopin but I'm wondering about Ativan? What would be a good suspension/solvent etc.. could I use water? Or would the drug sick to the side of the glass?

 

I don't think I can use full fat milk because Ativan is water soluble yes?

 

Any other other options? I tried PG I don't think I like it much. I was previously using vodka didn't really like that either but I think I like it better than the PG so I might have to switch back if there's no other options.

Hey Eric, I really like your idea, and that it's something that worked for you. Bob7 does something similar with micro crystalline cellulose to bulk out his benzo for easier weighing. Your method doesn't consider the added bulk of the crushed up pills, but maybe that gets lost in the noise. I definitely think a dry powder method like that could work well for people, but may also be dusty and depending on the bulking powder you use (I wouldn't use sugar as I don't eat any), you could still have settling problems. As with liquid, settling can be solved by stirring/shaking, so still a great idea. Out of place in the liquid benzo discussion, but I really appreciate hearing it!

 

SuperJess, I'm not experienced with Ativan, but most of the same rules and ideas with Klonopin should apply. Full fat milk has plenty of water in it, FYI.

 

My compounding pharmacist made me a mix of pure clonazepam with pure MCT oil, at my requested formula of 0.125mg/ml (1/4 of a 0.5mg pill per ml). It works well. Falls out of suspension in maybe fifteen minutes (even fresh out of the fridge), but drawing a dose is as easy as shake, draw, done; maybe 30 seconds tops and still plenty of good dispersion in that time-frame.

 

I believe this kind of oil suspension could be made easily at home. I have only made parts of the following formula myself in experimentation, parts I learned from a YouTube video on making pharmaceutical suspensions, and parts I learned from my pharmacist. I offer this as something to think about if you'd like to try an oil suspension; this is how I'd try to do it...

 

The tools to make a homemade MCT oil suspension would be a mortar and pestle, tablets, MCT oil, a medicine bottle with a syringe adapter (ideally) and a 1ml oral syringe that fits your adapter. Measure out your oil based on your desired formula (mg/ml), ideally in a graduated cylinder. Crush the appropriate number of pills in the mortar finely, then slowly add up to half of your oil and keep stirring the pestle to grind and suspend the tablet powder in the oil; take your time here to make sure you've got the pills thoroughly powdered and incorporated. Transfer the slurry to your medicine bottle. Add the remaining oil from the cylinder to your mortar, stir it around again and then add this to the bottle as well. Finally add the syringe adapter if you have one, cap and shake. Refrigerate, and it should last many weeks; easily 2-3 months.

 

On a liquid/tablet DMT I plan to use roughly 30ml of my 0.125mg clonazepam/ 1ml MCT oil over the course of 60 days.

 

The full fat milk thing supposedly only works with klonopin.  I've not heard of it working with Ativan.

 

Ativan's solubility in water is also very poor.  I think you'll have better luck dissolving into alcohol first then adding water.

Thanks badsocref!

 

Yes I had heard that before about Ativan not being good in milk.

 

I dropped a pill in water this am to test and it dissolved right away.. granted it is likely not evenly dispersed as it would be with alcohol (yes? Does alcohol make an evenly dispersed?)

 

And if it does dissolve in water you think I could just shake up the liquid and pull my dose right away?

 

I'm trying to find a way to do a DLMT.

 

The current formula I use it 1mg:2ml:8ml but I don't know how to change it to do a DLMT because it's such a small amount in the jar.

Hey SuperJess, ethanol, like PG and a few other chemicals, helps to dissolve some of the benzo into water, so yes, it would be more evenly dispersed in solution. It can't hurt to shake and pull your dose while everything is in some suspension.

 

I think your formula is 1mg of medicine in 10ml of solution, at 20% ethanol. Is that right? That's 0.1mg Ativan/ml. That's close to the ratio I use for DMT my clonazepam (I know their potency is different, so there's that); I use a 1ml oral syringe with 100 gradations (they're for sale on Amazon), so I can pull, like this morning, 0.65ml as part of my tapering schedule.

 

I use this site to create my taper schedule: http://benzo.alwaysdata.net/titration/titrationForm.php

 

If you want more volume (easier accuracy, maybe less storage stability), keep the Ativan to ethanol amounts the same, and bulk up that water dilution. If you do 1mg Ativan to 2ml ethanol to 98ml of water you'll get a 100ml solution with 0.01mg Ativan per ml. It's easier to do reductions with this much volume if you have less accurate syringes; also try to pull from the middle of the solution after shaking, to get some kind of an average suspension.

 

The same site I mention works with any dilution you want; just put it into the form!

 

EDIT: I wanted to add, the site I shared suggests 0.1mg/ml to do a DMT with Ativan. It's really not that hard with the 1ml syringes I described, plus with 20% ethanol in your mix you've got a decent refrigerator shelf-life for your solution.