Anybody here succeeded with water taper for K?

1) Those data points contradict every other published solubility ratio anywhere.  On that basis alone I would reject, or at least seriously question it validity.

2)  And if you look just a little farther down the page, you will see:

"Water Solubility 0.0176 mg/mL"

3) I feel reasonably confidant that those numbers are either a typo error, or more likely, a transcription error. When one data point is wildly at odds with tons of carefully researched and peer reviewed studies (and the standard tables that the pharma industry uses) , it would not seem prudent to  rely on what  is at best a questionable data point.  If I needed to create s reliable benzo solution, I would certainly NOT rely on any piece of that was inconsistent with all other reports.  And if  you use the widely published standard of 2ml for each 1mg, then the worst that can happen is you are using more solvent than necessary, so there is no risk using the "safe" number.  (But there is a real risk in using the outlier number!)

And finally, there are 4 Rx liquid benzos.  All 4 of them use  alcohol or PG as a solvent to create their product.  If benzos were in fact readily water soluble, why would the not just make a water based solution?

And  the Merck number (which is NOT really a Merck number anyway) offers no substantiated source, attribution, or validation.  At least with the Jouyban et.al. data, the process and research that supports the published data is included.

1) Those data points contradict every other published solubility ratio anywhere.  On that basis alone I would reject, or at least seriously question it validity.

 

2)  And if you look just a little farther down the page, you will see:

 

"Water Solubility 0.0176 mg/mL"

 

3) I feel reasonably confidant that those numbers are either a typo error, or more likely, a transcription error. When one data point is wildly at odds with tons of carefully researched and peer reviewed studies (and the standard tables that the pharma industry uses) , it would not seem prudent to  rely on what  is at best a questionable data point.  If I needed to create s reliable benzo solution, I would certainly NOT rely on any piece of that was inconsistent with all other reports.  And if  you use the widely published standard of 2ml for each 1mg, then the worst that can happen is you are using more solvent than necessary, so there is no risk using the "safe" number.  (But there is a real risk in using the outlier number!)

 

And finally, there are 4 Rx liquid benzos.  All 4 of them use  alcohol or PG as a solvent to create their product.  If benzos were in fact readily water soluble, why would the not just make a water based solution?

 

And  the Merck number (which is NOT really a Merck number anyway) offers no substantiated source, attribution, or validation.  At least with the Jouyban et.al. data, the process and research that supports the published data is included.

I have no reason to believe that the solubility data that I gave are typo's or transcription errors.

I would if you would have given me contradictory data but you have not.

You point out that this source:

https://www.drugbank.ca/drugs/DB00186

gives 2 different values for the water solubility of lorazepam, namely 80 mg/liter and 17.6 mg/liter, but these values are not contradictory, because, as I said in my previous post, the first, which is the Merck index(1996), is an experimental value and the second a predicted value, and it is the experimental value which counts and not the predicted value.

When you do not believe it is the Merck index, or believe it is a typo, see this source Jim Hawk gave:

http://www.benzobuddies.org/forum/index.php?topic=210792.msg2718406#msg2718406

It gives the same value and its source: O'Neil 2006, and when you click it you are referred to the Merck index.

There is no contradiction between a poorly water soluble drug substance and a solubility of 80 mg/liter, because this article calls it this way and still gives this value.

I am not denying that it is poorly water soluble but what I am saying is that it is possible to dissolve 1 mg lorazepam in 100 ml pure water at room temperature, when you give it enough time.

When you are still not convinced, this is a third source:

https://www.researchgate.net/publication/234954262_The_Improvement_of_Lorazepam_Solubility_by_Cosolvency_Micellization_and_Complexation

It says:

Lorazepam is an almost water insoluble substance. This study investigated the solubilization of lorazepam depending on media pH, cosolvents (ethanol, propylene glycol, polyethylene glycol 200 and 400)....... The main objective was to find the most suitable method for providing good solubility of this drug and thus its formulation in a liquid dosage form. Based on the results, the changes in the pH value of the media do not lead to a greater solubility of lorazepam . Of the cosolvents used, the greatest increase in solubility of lorazepam in water was achieved with ethanol.

It is a poor water soluble substance. The aqueous solubility of lorazepam is 0.0485 mg/ml (1.51 x 10-4 mol/L) .

So it gives a solubility of 48.5 mg/liter.

Figure 2 shows the depence of the solubility on the pH value.

This value differs from  80 mg/liter, maybe because they have not given it the minimal time to dissolve completely, but both values  are compatable with the possibility to dissolve 1 mg lorazepam in 100 ml of water.

You say;

And finally, there are 4 Rx liquid benzos.  All 4 of them use  alcohol or PG as a solvent to create their product.  If benzos were in fact readily water soluble, why would the not just make a water based solution?

First, I have never said that benzo's are readily water soluble, and the sources I quoted do not say it either, but still give the quoted values.

One of the reasons to use alcohol or propylene glycol is because their benzo concentration is about 1 mg/ml and I am making a 0.01 mg/ml concentration.

But I like this concentration. It allows me to use a 50 ml syringe and in this way I can work very accurately.

Next, because of the poor solubility I use water at room temperature, and do not keep it in the fridge.

Alcohol and propylene glycol have also preservative properties but I never keep my solution longer than 24 hours.

Because it is poorly soluble I wait 30 minutes after putting the tablet into the water, then shake it thoroughly for 10 to 15 seconds, and then wait again for 30 minutes.

After this time all sediment has fallen to the bottom, and when I draw out my solution now, leaving the sediment at the bottom,  it works the same as when I do a dry cut with a corresponding amount of lorazepam.

This is the proof for me that almost all lorazepam must have been dissolved, because when I do a dry cut I am clearly sensitive to changes of approximately 10 %

Excellent dissertation on why water titration is a bad idea.