Feedback: FAQs

[[bu...]]

soluble in.[/b]

 

No, it doesn't. Look again at the graph:

 

http://i9.photobucket.com/albums/a54/Seth_Ghiorse/Benzosolubility_zps599343c1.jpg

 

And again, you choose to ignore the difference between dissolution, and dilution.

 

When a solute is dissolved in a solvent,it undergoes a change in it its molecular structure, and changes from a discrete, granular solid, to a uniformly distributed liquid..

 

And when that solution is further diluted, the ratio (concentration) of solute:volume is changed.  But the initial solvency  ratios are unchanged.

[[Ho...]]

soluble in.[/b]

 

No, it doesn't. Look again at the graph:

 

http://i9.photobucket.com/albums/a54/Seth_Ghiorse/Benzosolubility_zps599343c1.jpg

 

And again, you choose to ignore the difference between dissolution, and dilution.

 

When a solute is dissolved in a solvent,it undergoes a change in it its molecular structure, and changes from a discrete, granular solid, to a uniformly distributed liquid..

 

And when that solution is further diluted, the ratio (concentration) of solute:volume is changed.  But the initial solvency  ratios are unchanged.

 

And again, builder, you discount my information where if you add a solvent the benzo is not soluble in, it could precipitate out of solution (also basic chemistry). You insist the benzo does not precipitate, but the solubility data previously supplied does not necessarily support that proposition.

 

Where is the data to support your claim?

[[Ho...]]

Hi HTDT,

 

Do you know what effects the other ingredients from the ground tablets have upon solubility of the active ingredients? What if binding agents also end up as solutes?

 

Nope, I have no idea.

 

I shake my solution before I pour out my dose into a graduated cylinder, to make sure all the particles are at least a bit mixed in. Is it a step I need to perform? I don't know. I could perform an experiment where I don't shake the solution, and only pour out the liquid, leaving all the particles on the bottom, to see how it has an effect on me (and it would be only me).

 

BUT... if my shaking works, why rock the boat?

 

For what it's worth, my 0.5 mg greenstone tablets mainly contain powdered cellulose (a filler) and corn starch (disintegrant and binder) (https://www.drugs.com/imprints/g-3720-7278.html). The other ingredients are probably 3% or less of the pill weight, if I remember my tablet manufacturing experience correctly.

[[Co...]]

Hi HTDT,

 

Do you know what effects the other ingredients from the ground tablets have upon solubility of the active ingredients? What if binding agents also end up as solutes?

 

Nope, I have no idea.

 

I shake my solution before I pour out my dose into a graduated cylinder, to make sure all the particles are at least a bit mixed in. Is it a step I need to perform? I don't know. I could perform an experiment where I don't shake the solution, and only pour out the liquid, leaving all the particles on the bottom, to see how it has an effect on me (and it would be only me).

 

BUT... if my shaking works, why rock the boat?

 

For what it's worth, my 0.5 mg greenstone tablets mainly contain powdered cellulose (a filler) and corn starch (disintegrant and binder) (https://www.drugs.com/imprints/g-3720-7278.html). The other ingredients are probably 3% or less of the pill weight, if I remember my tablet manufacturing experience correctly.

 

Shaking (immediately before measuring out the dose) is what I've always recommended. Though, to be careful to avoid a circular motion, as a vortex can/will introduce a concentration gradient for any ingredients not in solution.

[[bu...]]

 

And again, builder, you discount my information where if you add a solvent the benzo is not soluble in, it could precipitate out of solution (also basic chemistry). You insist the benzo does not precipitate, but the solubility data previously supplied does not necessarily support that proposition.

 

Where is the data to support your claim?

 

But, of course, benzo ARE  soluble in water, although, abeit, poorly soluble.  So diluting a solution made with a known solvent with water, does, in fact, (marginally) increase the effective solubility.

 

And you continue to ignore  my most important question. 

 

Someone is dependent on a drug that is, or will, cause both emotional and physical damage.  If a solution created with vodka (or PG) and water is NOT effective, so what?  A few days of discomfort and a return to the previous dosage??

 

I'll take that bet every time.

[[Co...]]

soluble in.[/b]

 

No, it doesn't. Look again at the graph:

 

http://i9.photobucket.com/albums/a54/Seth_Ghiorse/Benzosolubility_zps599343c1.jpg

 

And again, you choose to ignore the difference between dissolution, and dilution.

 

When a solute is dissolved in a solvent,it undergoes a change in it its molecular structure, and changes from a discrete, granular solid, to a uniformly distributed liquid..

 

And when that solution is further diluted, the ratio (concentration) of solute:volume is changed.  But the initial solvency  ratios are unchanged.

 

Builder. I'm no chemist. But, unless I am very mistaken, neither are you. So when you make an assertion regarding chemistry, and it does not chime with my (admittedly limited) knowledge, I will ask for you to back up your claims. However, you have failed to responded to the following comment from HopeToDoThis. Are you ignoring it?

 

That is incorrect. Once dissolved, a solute can become "undissolved" by the addition of an appropriate solvent that the solute is not soluble in.

 

One may be able to dissolve the benzo in alcohol. But then one adds water, a solvent the benzo is not soluble in. This can cause the benzo to precipitate out of solution.

 

In fact, "recrystallization" is a common method of purification.

 

This is why people ask for the data.

 

Again, I refer you to this graph, which you seem to accept as accurate (and I have no reason to doubt):

 

http://i9.photobucket.com/albums/a54/Seth_Ghiorse/Benzosolubility_zps599343c1.jpg

 

For alcohol/water mixtures, at a ratio in the order of 1:9, solubility is very low (a tiny, tiny fraction of what it is at 80-90% alcohol). How do you know that the benzodiazepine does not potentially recrystallize with the addition of water? Certainly, if we were to have the alcohol/water liquid already prepared (as with vodka, the oft suggested approach), the capacity for benzodiazepine going into solution is already very significantly diminished.

 

We could mitigate the potential problem by using a large enough volume of water to ensure that the benzodiazpine goes into solution (without saturating the liquid). But if we do this, what's the point of using alcohol at all?

 

Further, do the additional non-active ingredients also go into solution? If they do, surely we should expect some effect upon the ability of the liquid to also put the benzodiazepine into solution. But what effect, and to what degree? Similarly, what effects do the other chemicals in vodka have upon the potential for benzodiazepine going into solution?

 

I have loads of questions, and few answers. But since it is you (not just you, to be fair) who is making the claim for solubility and absolute assurance of there being no potential problems, it is also for you to back up your claims with reliable data.

 

Look. I am not against members attempting to make up such liquids. Some (but far from all) seem to have some success with them. The problem I have here are the absolute claims made for efficacy without any data. Worse, when challenged, the continued failure to address the specific questions and concerns.

 

Because of all these unanswered questions, I tend towards recommending suspensions over solutions. And for this reason, when preparing a 'solution', do not assume that it is in actuality a solution. Rather, assume that is at least a partial suspension and shake the contents immediately before extracting a dose would seem a sensible precaution.

 

One other possible precaution spring to mind: use pure ethanol instead of vodka. And it would not hurt to use distilled water too. However, the potential problems with the pill fillers remain. Besides, it is probably quite difficult to source pure ethanol.

 

So, how about some actual sources to back up what you are actually doing?

[[bu...]]

No, I'm not a chemist, but I still remember the fundamentals from high school chemistry. 

 

Once the structure of the solute has changed from discrete particulate to a uniformly distributed liquid, it will remain in that state.  The particulate structure can only be recovered by boiling off ("evaprorating") the liquid.

 

 

https://www.le.ac.uk/se/centres/sci/selfstudy/particle05.html

 

[[Co...]]

No, I'm not a chemist, but I still remember the fundamentals from high school chemistry. 

 

Once the structure of the solute has changed from discrete particulate to a uniformly distributed liquid, it will remain in that state.  The particulate structure can only be recovered by boiling off ("evaprorating") the liquid.

 

 

https://www.le.ac.uk/se/centres/sci/selfstudy/particle05.html

 

No, no, no. That's only (loosely) defining a solution. That is, it is a stable, homogeneous mixture of two chemicals. It has nothing to say about what happens when you introduce another solvent. Just because the solute might be recovered through evaporation, this does mean this is the only way that it my be precipitated from the solution.

 

https://en.wikipedia.org/wiki/Precipitation_(chemistry)

[[Ho...]]

No, I'm not a chemist, but I still remember the fundamentals from high school chemistry. 

 

Once the structure of the solute has changed from discrete particulate to a uniformly distributed liquid, it will remain in that state.  The particulate structure can only be recovered by boiling off ("evaprorating") the liquid.

 

 

https://www.le.ac.uk/se/centres/sci/selfstudy/particle05.html

 

No, that's not what it says.

 

It says, "Dissolving is a reversible process and the solute can be recovered from a solution by evaporation..."

 

There is no "only."

 

On another page (https://www.le.ac.uk/se/centres/sci/selfstudy/particle03.html) it says "Dissolving is a reversible process represented by considering particles mixing closely together and reversed by separating the particles."

 

That website is a study guide for teachers of young school children. It is not going to go into too much detail.

 

Unfortunately I can't find a webpage that discusses recrystallization in a manner that's not totally technical or totally boring. But I will keep trying.

 

But I myself have recrystallized chemicals. In one lab experiment, I did a chemical reaction of carbon-containing chemicals (a sub-field of chemistry called organic chemistry). As so often happens in such experiments, I ended up with brown goo at the bottom of the flask. I needed to purify the wanted chemical out of this brown goo.

 

So first I added warm methanol to dissolve the brown goo. Then I added ethyl acetate, and WOMP! While crystals formed at the bottom of the flask! I tell you it was like magic.

 

How do we know this doesn't happen with the addition of water to the benzo/alcohol solution? There's so little benzo we don't know if the white particles that form after adding water are only the tablet excipients or if the white particles contain drug?

 

Again, I think the point of the FAQ is to say, some people use the liquid taper with success. Some people don't.

[[Co...]]

 

Once the solute has been dissolved, further dilution does not alter the original solubility ratio.

 

That is incorrect. Once dissolved, a solute can become "undissolved" by the addition of an appropriate solvent that the solute is not soluble in.

 

One may be able to dissolve the benzo in alcohol. But then one adds water, a solvent the benzo is not soluble in. This can cause the benzo to precipitate out of solution.

 

In fact, "recrystallization" is a common method of purification.

 

This is why people ask for the data.

 

This is quite confusing to me. Very interesting, but mind blowing. Does this mean that this method is not really good to use? What I am discerning is that once water is added there might not be any Benzo? I am just trying to understand so that I can taper down the best possible way. Many years ago I did the water taper after doing cut and hold. That is all we had back then. I am glad that this is being discussed so that we can make the best decision for each one of us to get off. Thanks so much.

 

Hi Dana,

 

Sorry. Your post seemed to get a little lost in the mix. I think what you should take away from discussion is that if you are already using a method which works for you, then is little reason to change it. What's under discussion here are are some unequivocal unsubstantiated claims about various titration methods being 100% reliable while the proponents are unable to provide citations for their claims. We (BB) are in the process of trying to compile the best information there is about the subject, but also make clear what is unknown. There are unknowns regarding the solubility of ground benzodiazepine pills in alcohol/water mixtures. We have non chemists making patently erroneous claims about chemistry, and seemingly no understanding or appreciation of pharmacokinetcs and bioavailability. All these things come into the picture when we attempt to modify pills this way.

 

While it is safe to assume that there will be effects upon the medication by making up such liquids, this does not mean that it cannot work. The issue is really that we have little reliable data, so can provide no real numbers. The anecdotal evidence is mixed. Certainly many members who attempt titrating benzodiazepine liquids find that it works for them; but others report problems. Of course, different people use different preparations, so this complicates the picture even further.  In light of this, we advise caution. (Though I am not advocating for this) members might try to experiment with titration; this would be your decision.

 

To answer you question about what happens to the benzodiazepine after adding water: we are not sure. There is little reason to suppose that the benzodiazepine goes under a chemical change (is destroyed); though, I could not rule this out. What seems like a greater potential problem is that (assuming that the benzodiazepine actually goes into solution in the first place), is that all or some of the benzodiazepine falls out of solution, precipitating to again form a solid (crystals). Such crystals would probably tend to settle at the bottom of the liquid. That's no good when what we desire is uniformity of benzodiazepine in the liquid. It is for this reason I recommend shaking the liquid immediately before measuring out a dose. Not perfect, but it probably will help. (Though, be sure to not swirl the liquid, as this likely will induce a concentration gradient of benzo particles in the liquid - this would be very unhelpful). So, in short, the benzodiazepine will not disappear. But it might not be fully in solution. Personally, at this stage, I think a suspension medium would be a more reliable route.

[[Ho...]]

if V for example is soluble in water (0% etoh) , why dont we just dissolve at less than 0.04 mg/ml and skip the etoh? say dissolve a 10mgV in 1 liter of water? thats 0.01 mg/ml which is very far from the 0.04 limit and very convenient to compute. 

 

i failed my taper before but i was able to go down below 1mg from 8mg using the popular vodka/water method here. it seemed to be a good enough method to me.

 

if adding water after dissolving in etoh somehow does not make sure the benzo is still in a solution, then best we can do is do some agitation before pulling dose. and make small enough batches so that whatever fluctuations in the actual doses we get is small and even out quickly over a few days. this is further mitigated if you dose multiple times per day.

 

and whatever doubts we have about the other ingredients in the tablet being put in the home brew liquid, i think if we do the same procedure everytime then we are consistent in the amount of active ingredient we are getting everytime we make a batch.

 

the same doubts about the included non-benzo ingredients in the tablet could be said about those doing dry CnH. if you split a tablet into half how do you know you got half the potency of that tablet? the way people go about it is just consume the remaining split tablets within the next day to even out possible variance. if you want to be extreme you can weigh grided out tablet powder with a very sensitive digital jeweler's scale or something. i think if done correctly this is the best method but it seems tedious and the calibration and precision stuff intimidates me.

 

this issue is actually triggering to me. like many others i have been using the vodka/water method and it seems to be working fine. now i have another thing to worry about. i am probably replying here partly to ease my own fears and hopefully others' as well. what about us who cannot do CnH without intolerable suffering? in my particular case i only have access to 5mg V tabs and theres no liquid V available where i am from. earlier in my first taper attempt, i was at 5mg V and i thought i could handle 0.05mg cuts. i had lots of twitching and increased anxiety an i thought i could tough it out. fife days later i crashed and went back up. so i realized early on i could not even handle a 5% CnH style. so theres no other way for me than really small cuts of fractions of less than 1% in a day.

 

i hope this helps someone.

 

peace and healing to all sufferers, HS

[[Ho...]]

 

this issue is actually triggering to me. like many others i have been using the vodka/water method and it seems to be working fine. now i have another thing to worry about.

 

i hope this helps someone.

 

peace and healing to all sufferers, HS

 

HopeSurvives, I bolded the part of your message that really matters.

 

The more I read on these boards, the more I think the tapering is trial and error. You find what works. Some methods work for some people, other methods work for other people. I just read a post by one guy who says shaving pills is the only way to go. When I first saw the shaving pills with the scale method my first thought was "no way." (when I worked in a lab I hated weighing, especially small quantities, because it was so frustrating.) Instead, my liquid taper is working for me.

[[Ho...]]

from http://www.benzobuddies.org/forum/index.php?topic=97737.msg1714261#msg1714261

 

The following table shows the solubility of the various benzos in ethanol/water mixtures from 0% (i.e., plain water) to 100% ethanol.  Key: V=Valium; A=Ativan; Lib=Librium; K=Klonopin; X=Xanax.

 

Units = mg/ml

% Alc.  V          A        Lib      K          X

0        0.04    0.05    0.11    0.03    0.04

10      0.11    0.11    0.19    0.04 

20      0.21    0.23    0.29    0.08

30      0.57    0.77    0.80    0.20

40      1.90    3.51    2.89    0.60

50      4.76    4.19    7.48    1.43

60    11.17    8.04    12.48    2.64

70    21.31  13.09    22.89    4.22

80    28.67  17.33    31.81    5.65

90    38.36    6.64    31.72    6.18

100  26.07  10.89    19.46    5.11

 

===========================

 

using this data, V has solubility of 0.04 in pure water 0% etoh. if you use 10%etoh/90% water as solvent you have 0.11 solubility. so if i do the vodka and subsequent further dilution to water, i am doing something which is between these 2 values. the batch i make has actually only about 0.25% etoh overall. why dont i just call it 0% and just use the 0.04 solubility limit? again using this data, even if i just put my 10mgV tablet in a jar, crush it fine enough there with a spoon and add 1liter of water, i still have a solution with 0.01mg/ml strength.

 

 

builder, this is what i had in mind in the PM i sent you. why dont we just skip the alcohol and use this 0.04 pure water solubility. with this data it seems to me the etoh is just there to make sure the benzo dissolves first before diluting further in water. but then there is this doubt about coming out of solution once the water is added? using pure water is starting to look attractive to me now. and not taking any alcohol is better for our brains actually.

[[bu...]]

 

 

builder, this is what i had in mind in the PM i sent you. why dont we just skip the alcohol and use this 0.04 pure water solubility. with this data it seems to me the etoh is just there to make sure the benzo dissolves first before diluting further in water. but then there is this doubt about coming out of solution once the water is added? using pure water is starting to look attractive to me now. and not taking any alcohol is better for our brains actually.

 

If that makes you happy, then go for it.

 

I really have no axe to grind here.  I have often said that any procedure that  allows you to make small, gradual dose reductions, will work.

 

Fortunately, I had the advantage of Rx liquid (which specifies "dilute before using..."  (with no suggested limits on  dilutation ratios).

 

But if I had not had that advantage, I would certainly have chosen the "vodka method".  Water solubility is is marginal,  st best, and solubility in common solvents (the same ones pharma mfgrs use) is well established, and  reliable.  So my choice would always be start with a trusted solvent, and dilute to a convenient concentration/ratio (.1mg=1ml, or .01mg=1ml).

 

Dissolving your benzo in an appropriate solvent will make a uniformly-distribute solution

 

Diluting that solution with water  will change its concentration/ratio.  It will NOT change the actual solvency.  It will NOT "come out of solution".

 

And dissolution will NOT alter the basic chemistry or efficiacy of the underlyiing drug.

 

And when Colin asks me for citations, my reply will (again) be "learned it in high school chemistry"

[[pi...]]

 

 

builder, this is what i had in mind in the PM i sent you. why dont we just skip the alcohol and use this 0.04 pure water solubility. with this data it seems to me the etoh is just there to make sure the benzo dissolves first before diluting further in water. but then there is this doubt about coming out of solution once the water is added? using pure water is starting to look attractive to me now. and not taking any alcohol is better for our brains actually.

 

Hello HopeSurvives,

 

Please be aware that the PM system is to be used for chit chat and moral support only.  Advice about tapering and withdrawal support should be discussed on the open forum. 

 

Here is a link to the full guidelines about proper use of PM's:

 

http://www.benzobuddies.org/forum/index.php?topic=78011.0

 

pianogirl

[[...]]

 

Once the solute has been dissolved, further dilution does not alter the original solubility ratio.

 

That is incorrect. Once dissolved, a solute can become "undissolved" by the addition of an appropriate solvent that the solute is not soluble in.

 

One may be able to dissolve the benzo in alcohol. But then one adds water, a solvent the benzo is not soluble in. This can cause the benzo to precipitate out of solution.

 

In fact, "recrystallization" is a common method of purification.

 

This is why people ask for the data.

 

This is quite confusing to me. Very interesting, but mind blowing. Does this mean that this method is not really good to use? What I am discerning is that once water is added there might not be any Benzo? I am just trying to understand so that I can taper down the best possible way. Many years ago I did the water taper after doing cut and hold. That is all we had back then. I am glad that this is being discussed so that we can make the best decision for each one of us to get off. Thanks so much.

 

Hi Dana,

 

Sorry. Your post seemed to get a little lost in the mix. I think what you should take away from discussion is that if you are already using a method which works for you, then is little reason to change it. What's under discussion here are are some unequivocal unsubstantiated claims about various titration methods being 100% reliable while the proponents are unable to provide citations for their claims. We (BB) are in the process of trying to compile the best information there is about the subject, but also make clear what is unknown. There are unknowns regarding the solubility of ground benzodiazepine pills in alcohol/water mixtures. We have non chemists making patently erroneous claims about chemistry, and seemingly no understanding or appreciation of pharmacokinetcs and bioavailability. All these things come into the picture when we attempt to modify pills this way.

 

While it is safe to assume that there will be effects upon the medication by making up such liquids, this does not mean that it cannot work. The issue is really that we have little reliable data, so can provide no real numbers. The anecdotal evidence is mixed. Certainly many members who attempt titrating benzodiazepine liquids find that it works for them; but others report problems. Of course, different people use different preparations, so this complicates the picture even further.  In light of this, we advise caution. (Though I am not advocating for this) members might try to experiment with titration; this would be your decision.

 

To answer you question about what happens to the benzodiazepine after adding water: we are not sure. There is little reason to suppose that the benzodiazepine goes under a chemical change (is destroyed); though, I could not rule this out. What seems like a greater potential problem is that (assuming that the benzodiazepine actually goes into solution in the first place), is that all or some of the benzodiazepine falls out of solution, precipitating to again form a solid (crystals). Such crystals would probably tend to settle at the bottom of the liquid. That's no good when what we desire is uniformity of benzodiazepine in the liquid. It is for this reason I recommend shaking the liquid immediately before measuring out a dose. Not perfect, but it probably will help. (Though, be sure to not swirl the liquid, as this likely will induce a concentration gradient of benzo particles in the liquid - this would be very unhelpful). So, in short, the benzodiazepine will not disappear. But it might not be fully in solution. Personally, at this stage, I think a suspension medium would be a more reliable route.

 

Colin,

 

Thanks for your reply. It is good that this is being brought to our attention. I have been doing the DLMT, but one batch can vary to another. I have been swirling the liquid having no idea. I use PG and was wondering if that was the best agent for solution. Alcohol I can't use due to peptic ulcer disease.

Again, many years ago what I knew from the old forums was cut and hold which is alright at higher doses or was, crush the pills and make piles and taper or do a plain old water taper. I actually have done all 3. I have a friend from the old forum who crushed her pills, made piles and walked off at crumbs. She is doing fine today. It all depends. I may consider dry cutting with a scale. I have never done that, but know people here who do very well. We are all so individual with different circumstances. I really don't think there is that "Perfect Taper Method" out there. If there were, we would all be doing it. I took my share of chemistry and physics in college but forgot it all. I am grateful for this discussion, even though there are disagreements. It is really good to put some brilliant minds together to figure this out. I know it will help people make more informed decisions.

Thanks again for your response.

 

Dana

[[bu...]]

 

 

 

 

Hi Dana,

 

. There are unknowns regarding the solubility of ground benzodiazepine pills in alcohol/water mixtures. 

 

 

 

  (assuming that the benzodiazepine actually goes into solution in the first place),

 

 

There is no uncertainty  or lack of science and substantiation (which you uniformly choose to disregard).

 

There is a wealth of solubiliity data regarding benzos and various solvents published, and accessible with a simple google search in addition to the links I and others have already shared.

[[no...]]

Going to do builder a impromptu favor and list some sources for your reading pleasure, enjoy.

 

Solubility of chlordiazepoxide,diazepam,and lorazepam in ethanol+water mixtures at 303.2 K

https://kar.kent.ac.uk/29422/

 

Solubility of Benzodiazepines in Polyethylene Glycol 200 + Water Mixtures at 303.2 K

http://pubs.acs.org/doi/abs/10.1021/je900330p

 

Prediction of benzodiazepines solubility using different cosolvency models.

https://www.ncbi.nlm.nih.gov/pubmed/12164213

 

Prediction of benzodiazepines solubility using different cosolvency models.

Nokhodchi A1, Shokri J, Barzegar-Jalali M, Ghafourian T.

Author information

1

School of Pharmacy, Tabriz Medical Sciences University, Iran. nokhodchi@tbzmed.ac.ir

Abstract

The solubility of four benzodiazepines (BZPs) including diazepam (DIZ), lorazepam (LRZ) clonazepam (CLZ), and chlordiazepoxide (CHZ) in water-cosolvent (ethanol propylene glycol and polyethylene glycol 200) binary systems were studied. In general, increasing the volume fraction of cosolvents resulted in an increase in the solubility of benzodiazepines. The mole fraction solubilities were fitted to the various cosolvency models, namely extended Hildebrand approach (EHA), excess free energy (EFE), combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K), general single model (GSM), mixture response surface (MR-S). double log-log (DL-L), and linear double log-log (LDL-L). The results showed that DL-L model was the best model in predicting the solubility of all drugs in all the water-cosolvent mixtures (OAE% = 4.71). The minimum and maximum errors were observed for benzodiazepine's solubility in water-propylene glycol and water-ethanol mixtures which were 2.67 and 11.78%, respectively. Three models (EFE, CNIBS/R-K and LDL-L) were chosen as general models for solubility descriptions of these structurally similar drugs in each of the solvent systems. Among these models, the EFE model was the best in predicting the solubility of benzodiazepines in binary solvent mixtures (OAE% = 11.19).

 

will somebody proficient in scientific language please spell out to stupid peasant me what this bold part means? are they saying that h2o propylene glycol is better or worse than h2o alchol solvents for benzos?

 

or more simply, which is the best way to do the liquid benzo, as a solution or as a suspension?

 

...'cause i can easily make a suspension using this:

https://www.amazon.com/gp/product/B0773DL1XJ/ref=ppx_yo_dt_b_asin_title_o00_s00?ie=UTF8&psc=1

HUMCO 8916001 Flavor Blend 16 oz, Shape  5.0 out of 5 stars  ...undiluted....

 

(that i 've been using to make my seroquel suspension for over 6 months with NO PROBLEMS AT ALL)

 

it has the benefit of not needing refrigeration  (refrigeration can cause that precipitation separation crystalization thingee yall were talking about.)

the only "negative" is the price: $16.11 FREE One-Day Prime Shipping  ~ but it's still cheaper than Ora Plus or ora Pro. ~

[[Co...]]

Hi Dana,

 

. There are unknowns regarding the solubility of ground benzodiazepine pills in alcohol/water mixtures. 

 

 

 

  (assuming that the benzodiazepine actually goes into solution in the first place),

 

There is no uncertainty  or lack of science and substantion (which you uniformly choose to disregard).

 

There is a wealth of solubiliity data regarding benzos and various solvents published, and accessible with a simple google search in addition to the links I and others have already shared.

 

Interesting editing there, builder.

 

As for, "uncertainty or lack of science and [substantiation]", that's patently untrue. You have unreasonably applied strictly controlled laboratory experiments to your set of protocols, where the ingredients, methodology, apparatus and precautions clearly differ. Pills (with all their added ingredients) are not the same thing as the pure active ingredients used in the experiments; instead of pure ethanol, you use vodka. You also fail to understand the effects of adding second solvent (water) to the to the supposed (vodka) ethanol / benzo-pill solution, claiming, erroneously, that:

 

Once the structure of the solute has changed from discrete particulate to a uniformly distributed liquid, it will remain in that state.  The particulate structure can only be recovered by boiling off ("evaprorating") the liquid.

 

https://www.le.ac.uk/se/centres/sci/selfstudy/particle05.html

 

You have failed to respond to my and HopeToDoThis's critiques:

 

http://www.benzobuddies.org/forum/index.php?topic=231364.msg2970915#msg2970915

 

http://www.benzobuddies.org/forum/index.php?topic=231364.msg2970923#msg2970923

 

You have taken no account of chemistry, pharamacokinetics or bioavailability. Your claims regarding 'basic chemistry' are clearly incorrect. And since you have (as far as I can determine) never even mentioned pharmacokionetics or bio availability, and failed to respond to my questions regarding these, I can assume that you had not even heard of the terms until I mentioned them.

 

As for your quote of me at the top, let's try a full quote. Emphasised text reflect the excepts you used above. You know, context, and stuff. What I actually wrote:

 

Hi Dana,

 

Sorry. Your post seemed to get a little lost in the mix. I think what you should take away from discussion is that if you are already using a method which works for you, then is little reason to change it. What's under discussion here are are some unequivocal unsubstantiated claims about various titration methods being 100% reliable while the proponents are unable to provide citations for their claims. We (BB) are in the process of trying to compile the best information there is about the subject, but also make clear what is unknown. There are unknowns regarding the solubility of ground benzodiazepine pills in alcohol/water mixtures. We have non chemists making patently erroneous claims about chemistry, and seemingly no understanding or appreciation of pharmacokinetcs and bioavailability. All these things come into the picture when we attempt to modify pills this way.

 

While it is safe to assume that there will be effects upon the medication by making up such liquids, this does not mean that it cannot work. The issue is really that we have little reliable data, so can provide no real numbers. The anecdotal evidence is mixed. Certainly many members who attempt titrating benzodiazepine liquids find that it works for them; but others report problems. Of course, different people use different preparations, so this complicates the picture even further.  In light of this, we advise caution. (Though I am not advocating for this) members might try to experiment with titration; this would be your decision.

 

To answer you question about what happens to the benzodiazepine after adding water: we are not sure. There is little reason to suppose that the benzodiazepine goes under a chemical change (is destroyed); though, I could not rule this out. What seems like a greater potential problem is that (assuming that the benzodiazepine actually goes into solution in the first place), is that all or some of the benzodiazepine falls out of solution, precipitating to again form a solid (crystals). Such crystals would probably tend to settle at the bottom of the liquid. That's no good when what we desire is uniformity of benzodiazepine in the liquid. It is for this reason I recommend shaking the liquid immediately before measuring out a dose. Not perfect, but it probably will help. (Though, be sure to not swirl the liquid, as this likely will induce a concentration gradient of benzo particles in the liquid - this would be very unhelpful). So, in short, the benzodiazepine will not disappear. But it might not be fully in solution. Personally, at this stage, I think a suspension medium would be a more reliable route.

 

Since you have failed to provide any credible evidence to back up your absolute claims for efficacy, and have also failed to take on board any criticisms, questions or feedback, and instead continue to make the very same claims for efficacy in the very same unequivocal terms, I am now going to insist that you either change the language you use to describe the method you employ, or stop posting about titration.

 

There was really no need for it to be like this. In light that you cannot substantiate your claims, all it would have taken is a little self-reflection on your part, and back peddle a little. Just the acceptance that perhaps you should be less certain about your method, and that when some people provide feedback to you that your method did not work for them, pause for thought and consider that just maybe it is not quite as reliable and effective (for some at least) as you had supposed.

[[...]]

 

 

 

 

Hi Dana,

 

. There are unknowns regarding the solubility of ground benzodiazepine pills in alcohol/water mixtures. 

 

 

 

 

  (assuming that the benzodiazepine actually goes into solution in the first place),

 

 

There is no uncertainty  or lack of science and substantion (which you uniformly choose to disregard).

 

There is a wealth of solubiliity data regarding benzos and various solvents published, and accessible with a simple google search in addition to the links I and others have already shared.

 

Builder,

 

I am reading these links and find them very credible. All of you have presented excellent points and great evidence that I could have never found. Even though there are differing opinions on this, I am never too old to learn and am grateful for your sharp minds. Very much appreciated!

[[bu...]]

 

or more simply, which is the best way to do the liquid benzo, as a solution or as a suspension?

 

 

 

 

A solution will guarantee that the the benzo in your solution will be uniformly distributed, and that every ml of liquid will contain exactly the same amount of benzo.

 

OTOH, a suspension will be a randomly distributed liquid, no guarantee of uniformity.

 

When folks put together a microtaper plan, they see all these numbers in .1, .01. even .001mg, and think that accuracy and precision are required to do a microtaper.  But a microtaper is really about a gradual reduction, NOT a precise reduction

 

Obviously, a uniformly-distributed solution will be the most reliable choice, but  for most folks, a suspension made with a quality pharma grade suspension agent will work just fine

[[Fi...]]

I don't wish to interrupt a good debate but I'm reminded of a story:

 

Two rams were butting heads to establish dominance. After a few rounds, a cute ewe snuggled up to one of the rams. He looked over and said: "Not now, I have a headache."

 

Badda Bing, Badda Boom ... carry on

[[Ho...]]

I'm not going to argue anymore. But I think my bachelor degree in chemistry and 15+ years as a quality control chemist in the pharmaceutical industry should mean something. And no I'm not a pharma shill. The industry certainly has its faults.

 

nomoredrugsforme, when they say "error" what they mean is the difference between what their theoretical model predicts and what experimental measurements actually measured.

[[no...]]

I'm not going to argue anymore. But I think my bachelor degree in chemistry and 15+ years as a quality control chemist in the pharmaceutical industry should mean something. And no I'm not a pharma shill. The industry certainly has its faults.

 

nomoredrugsforme, when they say "error" what they mean is the difference between what their theoretical model predicts and what experimental measurements actually measured.

 

i place more weight in the experience of a degreed chemist with 15+ years as a quality control chemist in pharmaceuticals, than i do in a layperson's opinion.

 

so

The minimum and maximum errors were observed for benzodiazepine's solubility in water-propylene glycol and water-ethanol mixtures which were 2.67 and 11.78%, respectively.

actually means there's a big whoppin difference in what the scientists thought would be and what it actually was, referring to solubility of benzo in the 2 different solvents. food for thought.

 

 

[[Ho...]]

 

so

The minimum and maximum errors were observed for benzodiazepine's solubility in water-propylene glycol and water-ethanol mixtures which were 2.67 and 11.78%, respectively.

actually means there's a big whoppin difference in what the scientists thought would be and what it actually was, referring to solubility of benzo in the 2 different solvents. food for thought.

 

Theories for predicting solubilities are only used as a starting point. Science is really about measured data. The theories have to explain the data. If a theory doesn't fit with the data, then the theory must get tossed. These guys are saying their theory matches pretty well with the real world by saying that the difference between what their theory says and what is real is pretty close. I wonder what other "peers" think of their claim.

 

Oh boy now my brain hurts.