Daily Micro-Tapering Support Group

[[ga...]]

 

Hi SG and Gardner,

 

Interesting about the conflicting solubilities for L.  SG, I agree that the Jouyban study was to predict the solubility of other benzos by using their model.  I am not sure his group actually determined the solubility of L. I would need to read the papers again. I also agree that the data from the drug company should be valid, but I also wonder about "approximate." It would be helpful to see the study and the analysis with statistics.  Sorry, I accidentally hit save and this posted before I finished.

 

As far as the L not being stable in solution, I would think that means it starts to decompose. I have not looked at the structure or physical properties, so at this moment cannot comment on that possibility. For example, Vitamin C is not stable when exposed to air, heat, or light.  I have to look at the properties and the structure before making any comment on the stableness of L in water. We have been very busy at school, so I am not sure if I will have time until over the weekend. I would also like to ask one of my colleagues (organic chemist) about this.

 

That's what I was afraid it was saying. Yikes! I would love, love, love to hear the answer to this. I have a Librium titration in my future. Thanks so much for looking into this, Anne. I have not found much at all on the board about experience with Librium.

 

Hope school is going well for you this year. I used to teach, only grade school, but really miss it. Each year was a whole new adventure with my little semi-formed human beings!

 

Gard

 

Hi Gardner,

 

I wouldn't worry about it.  As SG said, many have tapered L in the past with water or alcohol.  I will ask my colleague what he thinks though. The problem is he doesn't come in to work often.  I know I should see him sometime next week though. Regardless, I am confident you will do fine with it.  Being not stable in solution could mean that it decomposes over several days or over a few weeks time. We just don't know.  Also, what "solution" does the reference refer to?  Is water the solvent, alcohol, or something else?  It could be that one type of solution is more stable than another.

 

Again, I would not worry about it.  Too many others have done a liquid titration with L. 

 

Have a great night!!

Anne

 

Thanks, Anne. Lucky for me (or not lucky) I have a long way to go with tapering my alprazolam intensol before I have to figure out my Librium. I thought I was going to have to start dissolving my Librium sooner, but SG suggested I just take it 5 times/day instead of 2 or 3 times since I take 25mg and have 5mg capsules. Can't believe I didn't think of that!

[[...]]

Gard,

 

There was a BB member named Oscar who liquified L with plain water, I believe.  He did that for a long time and as far as I know it went fine.  You could look up his old posts.  I really think there is nothing to fear here.  It will only be in liquid a few hours.  And, as Anne said, we don't even know what type of liquid they were referring to.  Also, even if it did decompose a little...by a few percent...your body would adjust to that as it would be like a cut.

 

Anne,

 

Yes, Jouyban is hard to ignore.  It was a solid study and data set and a solubility of 2mg/ml just does not fit with the rest.  I'll go back a recheck though, just to satisfy my own doubt.  It is also hard to ignore Hoffmann-LaRoche chemists who measured it as 2mg/ml. What did they mean by "approximate"?  I notice they did not report it as 2.0mg/ml...they said "2".  Did they just ballpark it?

[[an...]]

Gardner,

 

I agree with SG, there is nothing to worry about.

 

SG

 

They reported it as just a "2"?  No units?  That could mean anything. Do you have a link to the reference?  I can't imagine that they just ballparked it.  They would have done solubility studies. That would have been very basic. Not sure what they mean by approximate though. A range is usually reported.  I would think that approximate would be very close to the actual solubility though.

 

Thanks

Anne

[[...]]

Oh, I meant "2mg/ml".  They did not report it to the first decimal place, so does that reflect on the accuracy of the test they did I wonder?  Kind of and odd way to report a measured value.  Typically I'd think at least two digits would be reported, but I agree that it is hard to believe they were not reasonably accurate.  Here is the link...

 

https://books.google.com/books?id=ghZjsAPDO58C&pg=PA39&lpg=PA39&dq=Macdonald,+a.,+a.f.+michaelis,+and+b.z.+senkowski&source=bl&ots=pBtzY4iPeb&sig=0krDmb3DYbnShDs2gX5ItWEv4q0&hl=en&sa=X&ved=0CCYQ6AEwAmoVChMIgZTInaHlyAIVARoeCh0LiA0K#v=onepage&q=Macdonald%2C%20a.%2C%20a.f.%20michaelis%2C%20and%20b.z.%20senkowski&f=false

 

Go to section 2.9 on p. 25.  In that same table they report solubility in 95% ethanol as 23mg/ml, which is in pretty good agreement with Jouyban, who measured 26mg/ml.

 

In that link I just noticed the next section is on "chlordiazepoxide HCl."  Solubilities are much higher for that substance.  How is that different from plain chlordiazepoxide?  The chemistry is getting beyond me.

[[ga...]]

Gardner,

 

I agree with SG, there is nothing to worry about.

 

SG

 

They reported it as just a "2"?  No units?  That could mean anything. Do you have a link to the reference?  I can't imagine that they just ballparked it.  They would have done solubility studies. That would have been very basic. Not sure what they mean by approximate though. A range is usually reported.  I would think that approximate would be very close to the actual solubility though.

 

Thanks

Anne

 

Anne and SG, I'm OK right now, because I am going to just take the middle-of-the-night pill with a cat piller so I don't drop and lose it. But, when I need to liquify my L to taper it, I will need one of my kids to come home on the weekend and set up all my meds for the whole week. So the L will be in a liquid form for that long. 

[[...]]

Anne and SG, I'm OK right now, because I am going to just take the middle-of-the-night pill with a cat piller so I don't drop and lose it. But, when I need to liquify my L to taper it, I will need one of my kids to come home on the weekend and set up all my meds for the whole week. So the L will be in a liquid form for that long. 

 

You should be able to get the lowdown on L liquids from someone here.  I have not seen Oscar around for quite some time, but there has to be others.  It is a common worry for all benzos, not just L.  Personally I think it is a good idea to keep the time in liquid short...like a few days...since we are creating our own liquids and have no info on long-term effects.  Although if you try longer periods and it works, then that is proof.

[[...]]

This is from the Jouyban L paper.  Looks like careful work to me.  Each measurement was repeated three times.  I have confidence in these results.  The temp used was a little warm above room temperature...86 degrees.

 

Apparatus and Procedures. The binary solvent mixtures were prepared by mixing the appropriate volumes of the solvents with the accuracy of 0.001 volume fraction. The solubility of benzodiazepines in ethanol + water mixtures was determined by equilibrating excess amounts of the solids at 303.2 K using a shaker (Behdad, Tehran, Iran) placed in an incubator equipped with a temperature-controlling system maintained constant within ( 0.2 K. After a sufficient length of time (> 24 h), the saturated solutions of the drugs were filtered using hydrophilic Durapore filters (0.45 μm, Milipore, Ireland), diluted with methanol, and then assayed at 234 nm, 231 nm, and 231 nm,

respectively for chlordiazepoxide, diazepam, and lorazepam using a UV-vis spectrophotometer (Beckman DU-650, Fullerton). The preliminary investigations showed that the filter did not absorb the solutes through the filtration process. Concentrations of the diluted solutions were determined from the calibration curves. Details of calibration curves are shown in Table 3. Each experimental data point represents the average of at least three repetitive experiments with the measured mole fraction solubilities being reproducible on a relative basis within ( 4.2%. The standard relative deviations of mole fraction solubilities ranged from 1.0 % to 6.6 %. The densities of the

saturated solutions were determined using a 5 mL pycnometer with the uncertainty of (σn-1 ) 0.003 to σn-1 ) 0.018) g ·cm-3.

[[Co...]]

Hi Everyone,

I've been hanging out over on the klonopin klub thread and it was suggested I stop by here and get some advice on my taper.  I'm at .375 mg and ready to do a 5% cut. 

Thanks all and I hope everyone is having 'well' moments.

[[...]]

Hi Everyone,

I've been hanging out over on the klonopin klub thread and it was suggested I stop by here and get some advice on my taper.  I'm at .375 mg and ready to do a 5% cut. 

Thanks all and I hope everyone is having 'well' moments.

 

Well, if you want to cut smaller you are in a good position to do that being on .375mg K.  What did you have in mind?

[[an...]]

This is from the Jouyban L paper.  Looks like careful work to me.  Each measurement was repeated three times.  I have confidence in these results.  The temp used was a little warm above room temperature...86 degrees.

 

Apparatus and Procedures. The binary solvent mixtures were prepared by mixing the appropriate volumes of the solvents with the accuracy of 0.001 volume fraction. The solubility of benzodiazepines in ethanol + water mixtures was determined by equilibrating excess amounts of the solids at 303.2 K using a shaker (Behdad, Tehran, Iran) placed in an incubator equipped with a temperature-controlling system maintained constant within ( 0.2 K. After a sufficient length of time (> 24 h), the saturated solutions of the drugs were filtered using hydrophilic Durapore filters (0.45 μm, Milipore, Ireland), diluted with methanol, and then assayed at 234 nm, 231 nm, and 231 nm,

respectively for chlordiazepoxide, diazepam, and lorazepam using a UV-vis spectrophotometer (Beckman DU-650, Fullerton). The preliminary investigations showed that the filter did not absorb the solutes through the filtration process. Concentrations of the diluted solutions were determined from the calibration curves. Details of calibration curves are shown in Table 3. Each experimental data point represents the average of at least three repetitive experiments with the measured mole fraction solubilities being reproducible on a relative basis within ( 4.2%. The standard relative deviations of mole fraction solubilities ranged from 1.0 % to 6.6 %. The densities of the

saturated solutions were determined using a 5 mL pycnometer with the uncertainty of (σn-1 ) 0.003 to σn-1 ) 0.018) g ·cm-3.

 

Yes, I agree. It was carefully executed. I have no problem with this. Also, if I remember correctly this is a peer reviewed journal article.

[[Co...]]

Hi SG,

I would like to cut 5%.  I believe it might be (on the gram scale) .121 grams? 

.375 mg = .127 g on my scale.

[[...]]

Hi SG,

I would like to cut 5%.  I believe it might be (on the gram scale) .121 grams? 

.375 mg = .127 g on my scale.

 

Yes, those numbers all make sense to me.  .121g is 5% of .127g so that would be a 5% cut.  You can do what you want, but I'd encourage you to break the 5% into smaller cuts as it will be easier on you even though the rate won't change.

[[...]]

Yes, I agree. It was carefully executed. I have no problem with this. Also, if I remember correctly this is a peer reviewed journal article.

 

Yes, it was a peer-reviewed journal.

 

J. Chem. Eng. Data, 2009, 54 (7), pp 2142–2145

DOI: 10.1021/je900200k

Publication Date (Web): April 22, 2009

Copyright © 2009 American Chemical Society

[[Co...]]

Ok SG, what do you suggest?  As long as I don't have to figure out the math 

[[an...]]

Oh, I meant "2mg/ml".  They did not report it to the first decimal place, so does that reflect on the accuracy of the test they did I wonder?  Kind of and odd way to report a measured value.  Typically I'd think at least two digits would be reported, but I agree that it is hard to believe they were not reasonably accurate.  Here is the link...

 

https://books.google.com/books?id=ghZjsAPDO58C&pg=PA39&lpg=PA39&dq=Macdonald,+a.,+a.f.+michaelis,+and+b.z.+senkowski&source=bl&ots=pBtzY4iPeb&sig=0krDmb3DYbnShDs2gX5ItWEv4q0&hl=en&sa=X&ved=0CCYQ6AEwAmoVChMIgZTInaHlyAIVARoeCh0LiA0K#v=onepage&q=Macdonald%2C%20a.%2C%20a.f.%20michaelis%2C%20and%20b.z.%20senkowski&f=false

 

Go to section 2.9 on p. 25.  In that same table they report solubility in 95% ethanol as 23mg/ml, which is in pretty good agreement with Jouyban, who measured 26mg/ml.

 

In that link I just noticed the next section is on "chlordiazepoxide HCl."  Solubilities are much higher for that substance.  How is that different from plain chlordiazepoxide?  The chemistry is getting beyond me.

 

I see. Thank you for providing the link. The number of significant figures reported depends on the measuring devices that were used for the study.  This is only 1 significant figure.  I imagine that they were not concerned with high accuracy. I am surprised that a range was not provided though. I am sure the value represents what they determined as the solubility.

 

As for the chlordizepoxide HCl. Most drugs are either weak acids or bases. For example, amines are weak bases, and many drugs are administered as amine salts. These salts are usually odorless white crystalline solids.  They are much more soluble in water than a neutral amine.  When administered as a salt, the solubility and dissolution rate of the drug is increased. This is because they are ionic and will dissolve well in aqueous fluids. Diphenhydramine is an antihistamine (found in medications) that is a liquid--it is very oily. When converted to an amine salt it is formulated into  medication. Benadryl is diphenhydramine hydrochloride. which is represented as (C₆H₅)₂CHOCH₂CH₂NH(CH₃)₂⁺ Cl^-

 

 

 

 

 

[[ga...]]

Hi SG,

I would like to cut 5%.  I believe it might be (on the gram scale) .121 grams? 

.375 mg = .127 g on my scale.

 

Yes, those numbers all make sense to me.  .121g is 5% of .127g so that would be a 5% cut.  You can do what you want, but I'd encourage you to break the 5% into smaller cuts as it will be easier on you even though the rate won't change.

 

:thumbsup:

 

This is called the micro-tapering thread because we make micro-cuts every day instead of big cuts every 2 weeks. And trust me, you want SG doing your math, not me! He is one of the math gurus. I am the try-to-make-my-taper-as-weird-as-possible-and-then-ask-for-help non-guru.

 

Gard

[[ga...]]

This is from the Jouyban L paper.  Looks like careful work to me.  Each measurement was repeated three times.  I have confidence in these results.  The temp used was a little warm above room temperature...86 degrees.

 

Apparatus and Procedures. The binary solvent mixtures were prepared by mixing the appropriate volumes of the solvents with the accuracy of 0.001 volume fraction. The solubility of benzodiazepines in ethanol + water mixtures was determined by equilibrating excess amounts of the solids at 303.2 K using a shaker (Behdad, Tehran, Iran) placed in an incubator equipped with a temperature-controlling system maintained constant within ( 0.2 K. After a sufficient length of time (> 24 h), the saturated solutions of the drugs were filtered using hydrophilic Durapore filters (0.45 μm, Milipore, Ireland), diluted with methanol, and then assayed at 234 nm, 231 nm, and 231 nm,

respectively for chlordiazepoxide, diazepam, and lorazepam using a UV-vis spectrophotometer (Beckman DU-650, Fullerton). The preliminary investigations showed that the filter did not absorb the solutes through the filtration process. Concentrations of the diluted solutions were determined from the calibration curves. Details of calibration curves are shown in Table 3. Each experimental data point represents the average of at least three repetitive experiments with the measured mole fraction solubilities being reproducible on a relative basis within ( 4.2%. The standard relative deviations of mole fraction solubilities ranged from 1.0 % to 6.6 %. The densities of the

saturated solutions were determined using a 5 mL pycnometer with the uncertainty of (σn-1 ) 0.003 to σn-1 ) 0.018) g ·cm-3.

 

Yes, I agree. It was carefully executed. I have no problem with this. Also, if I remember correctly this is a peer reviewed journal article.

 

I am very impressed that y'all have a clue what this is talking about! I read it but… 

All I can gather is that whoever wrote this was a very, very careful person, which is a very good quality in a researcher.

[[Ma...]]

SG,

I am starting my c/o tonight. For my last dose I am adding 3mg of V for . 15mg of K. I know I said I would add to morning and night, but I decided to just do one dose at first. I felt more comfortable doing that because my body in the past has not liked when I have changed several doses. I am more cautious right now because of my stomach. I will reevaluate in 2 days and probably add the same to the dose that is 12 hours from this one. That is OK, right? I know for 3mg of K to V, Ashton switches one dose . 5mg of K for 10mg of V every week for two weeks. Then she starts adding 5mg of V for .5 mg of K. My stomach and sleep still have not been good. My stomach in is doing OK now. I am hoping I get some sleep and my stomach doesn't wake me up. I have not being have any other issues. Cutting or holding have both made no difference. My acupuncturist is helping. I had a question about dosing. I always dosed at set times of the day. More recently, when the interdose wd became really horrible, I started dosing every 3 hours. Dosing times are pretty similar each day. Do you think it would be better to have set times again? The average weight for my 10mg V pills was . 150g. They were much more consistent in weight than my K pills. They also weigh less. My . 5mg pills avg weight is.169g and 1mg.174g. Is that normal? Thank you you so much!

 

XO Maya

[[...]]

Ok SG, what do you suggest?  As long as I don't have to figure out the math 

 

No math, it's easy.  You're using a scale and have .5mg pills.  The smallest cut you can make is ~.003mg.  At your dose I'd recommend beginning by cutting .001mg K per day to get you bearings.  This would be a cut of .001g on the scale every three days, so you would cut, hold two day, cut, hold two days...in that pattern.  I'd do this for a few weeks to get the feel for it and see how it goes.  If all is good you can think of increasing.

[[Co...]]

I think my little brain can handle that SG.  Just to make sure because I'm freakin neurotic -  I'm currently at .127g, cutting .001g would be .126g and then .125g etc.? 

[[ga...]]

Yay, Maya!!!

 

Pssst. Don't worry, you can do this, nerves and all! My son is at his 21st birthday party right now and I am waiting up to see if his "friends" succeeded in getting him sloshed for the first time. It's gonna be a long night. We can be paranoid together.  

[[ga...]]

I think my little brain can handle that SG.  Just to make sure because I'm freakin neurotic -  I'm currently at .127g, cutting .001g would be .126g and then .125g etc.?

 

Coyote, you are in good company. We do paranoid really well around here. Or at least I do! 

 

I officially invite you to our Club Paranoia. Maya is finally able to start her crossover tonight; I just did a big switch of my meds which has knocked me off balance; and my son is out hopefully not getting drunk right now on his first official day to be legally drinking. So come on in and join us!

 

Gard

[[Ma...]]

Thank you, Gardener!

 

You are always so wonderful and supportive! I hope you are doing ok with rearranging your doses. For me I try to rearrange them not all at once. For me, my body gets confused with too many changes. I know others are different. I also have the whole rapid metabolizer issue etc. I have also have had to hold a couple days after making changes. It seems like it will be much better for you. I am foggy and tired. I also haven't been on BB much last night or today. I do see a lot of science talk about L. I don't try to understand it, but I know you will be fine. I hope things are going well with your appts. I hope your son has a fun birthday, but not too much fun! Sending you lots of love, my sweet friend!

 

XO Maya 

 

Coyote,

I am glad you came over and talked to SG. He will help A LOT! You will do great!

 

 

[[ga...]]

Thank you, Gardener!

 

You are always so wonderful and supportive! I hope you are doing ok with rearranging your doses. For me I try to rearrange them not all at once. For me, my body gets confused with too many changes. I know others are different. I also have the whole rapid metabolizer issue etc. I have also have had to hold a couple days after making changes. It seems like it will be much better for you. I am foggy and tired. I also haven't been on BB much last night or today. I do see a lot of science talk about L. I don't try to understand it, but I know you will be fine. I hope things are going well with your appts. I hope your son has a fun birthday, but not too much fun! Sending you lots of love, my sweet friend!

 

XO Maya 

 

Coyote,

I am glad you came over and talked to SG. He will help A LOT! You will do great!

 

Hi Maya. I'm so glad you are feeling well enough to try the crossover and I pray it brings you some relief.  Mine brought me my first window in a month, so I'm very hopeful for you! I did feel tired and depressed for a few days with each switch, but it lifted and then I would cross a little bit more. I'm trying to keep tapering my X now, but sometimes wonder if I should have kept going with the cross. The X has always been brutal for me and maybe I'd be better with it gone. But, hey, we in Club Paranoia aren't going to do any more crossing than we have to.

 

I did the recent big switch because I showed my tapering schedule to SG and he pointed out that I was dosing very unevenly in my half-crossed X/L state. I had not figured in the half-lives when I created my schedule and what I was doing was making no sense. We figured out that the easiest way to keep my blood levels even in my half-X half-L state was to dose each of them 5 times/day. But that meant I had to figure out how to take my 5mg L capsule (tiny little thing) in the middle of the night without dropping it and losing it. Since when I drink my bedside X liquid in the night I sometimes drop and lose the bottle cap, which is much bigger than the L capsule, I needed a drop-proof plan for that itty bitty capsule. Here it is!

 

 

Don't worry. I plan to practice this until I'm sure I can do it half asleep and not choke! 

 

We can do this!! (I say sounding braver than I feel! )

 

So…I wonder what time 21-year-olds come home from their birthday parties, anyway?? Not that I'm paranoid or anything!!

 

 

XXOO

[[...]]

I see. Thank you for providing the link. The number of significant figures reported depends on the measuring devices that were used for the study.  This is only 1 significant figure.  I imagine that they were not concerned with high accuracy. I am surprised that a range was not provided though. I am sure the value represents what they determined as the solubility.

 

As for the chlordizepoxide HCl. Most drugs are either weak acids or bases. For example, amines are weak bases, and many drugs are administered as amine salts. These salts are usually odorless white crystalline solids.  They are much more soluble in water than a neutral amine.  When administered as a salt, the solubility and dissolution rate of the drug is increased. This is because they are ionic and will dissolve well in aqueous fluids. Diphenhydramine is an antihistamine (found in medications) that is a liquid--it is very oily. When converted to an amine salt it is formulated into  medication. Benadryl is diphenhydramine hydrochloride. which is represented as (C₆H₅)₂CHOCH₂CH₂NH(CH₃)₂⁺ Cl^-

 

That's interesting.  So does that mean Librium can be made into chlordiazepoxide HCl to dissolve better in water, yet still essentially be Librium in the body?  Is chlordiazepoxide HCl still Librium?  I've noticed a lot of drugs have "HCl" at the end of their names.