Reusing syringes with a milk titration + discussion on lorazepam water titration

[[po...]]

As I am titrating with milk, I throw my syringes away when I am done preparing my daily dose. However, I wonder if it would be safe to instead rinse them with distilled water, draw some 70-80% alcohol solution inside, let it sit anywhere between 5 to 30 minutes, then allow the syringe to dry after that?

 

Normally, I would wash the syringe (plunger removed) with hot water and soap, but I am bedridden so I cannot get up to the sink to do this.

[[Li...]]

I have not studied this topic in depth but my understanding is that most syringes have a lubricant (e.g.silicone oil or a custom coating) on the inside of the barrel that facilitates gliding of the plunger during use.  My guess is that rinsing the syringe with an alcohol-based solution might hasten the degradation/elimination of this lubricant. 

 

My personal experience is that rinsing a syringe with distilled water several times after use then air drying the barrel and plunger keeps the syringe ‘clean enough’ and ‘functional enough’ for multiple uses. When the plunger stops gliding smoothly, I replace the syringe with a new one. 

 

However, let me hasten to add that I do not have personal experience using syringes with a homebrew liquid made with milk.  We have at least two currently active members who do so I hope they will share their thoughts and experiences.

 

Notes (if you decide to reuse):

 

(1) I’ve read that some members store their syringe(s) in the refrigerator between uses in an effort to minimize microbial growth.

 

(2) The numbers on the syringe barrel begin to wear off after multiple uses.  Placing a piece of clear tape over the numbers prevents this.

 

[[gr...]]

Hi potato, In your signature it looks like you are using the diazapam oral solution, if that is the case you do not need to use milk you can just  use water. It will mix evening and perfectly with water. No need to use milk...

[[po...]]

Thank you, Libertas. Jerky needles are difficult to use, so best not wear the oil coating off with alcohol. Microbial growth is my concern, but I wouldn’t be able to put my syringes in the fridge as it is in the kitchen (far from my bed). I will probably just use new syringes every time — I really don’t want to risk a gastrointestinal infection, as I am particularly sensitive to these (they have significantly worsened my chronic illness, twice).

 

gray cloud: I am afraid that your advice is misguided. I have written a review on suitable solvents for diazepam oral solutions, because diazepam is insoluble in water. It cannot “mix even[ly] and perfectly with water”. I invite you to read the why and how: http://www.benzobuddies.org/forum/index.php?topic=267260.msg3372864#msg3372864

 

(You may also be interested in reading my exchange with confuseduser on the following page of the topic.)

[[gr...]]

I was under the impression that you were using the Diazepam intensol which is a solution.  I am using the lorazepam intensol and it mixes perfectly and evenly with water.  I have not had a problem with it and I do not shake it when I take my dose.  Guess maybe the Diazepam is different....  The liquid is working so much better for me than the pills were....

[[po...]]

Neither diazepam nor lorazepam are (practically) soluble in water. Indeed, the Intensol solutions are that; solutions. However, once diluted with water, the lorazepam-water mixture is a suspension, not a solution. It is not even and perfect: lorazepam particles in the water are of different sizes, and either float around unevenly or sink to the bottom. The latter is especially likely to happen if the mixture is not shook well and if it is let to sit after shaking.

 

None of this matters if you consume all of the lorazepam that you dosed from the Intensol vial, as you are then ingesting exactly the dose that you measured from the vial. This and masking the taste of the solution are the reasons why the Intensol package leaflet recommends mixing it with a liquid or semi-solid food. On the other hand, if you remove some of this mixture with a syringe for your taper, you cannot be sure that you are removing the intended amount of lorazepam. How much lorazepam is removed depends on the amount and sizes of lorazepam particles in the part of the liquid that you draw from with the syringe; there could be close to no particles, the amount you want, or too many.

 

Many people have indeed successfully tapered with a suspension made from diluting an oral benzodiazepine solution in water, but this practice carries some potential risks (namely, uneven dosage reductions) that people should be informed of so that they may decide whether these risks are acceptable to them. I am glad that you have found success in diluting your lorazepam oral solution in water, and I hope it will continue to get you through the tail end of your taper more smoothly. Personally, I have chosen to use whole milk as it is a decent solvent for diazepam (I do not know if that is the case for lorazepam).

 

PS: as you may glean from this research article, formulating an oral lorazepam solution is not straightforward. https://www.sciencedirect.com/science/article/pii/S0928098717300490

[[gr...]]

I am not taking the entire batch that I make. I am taking individual doses from it. I am not having any problems with it. I do not see particles floating in it and it is staying crystal clear. So I am really not sure.

[[gr...]]

I just called West Ward the maker of Lorazepam intensol and they informed me that when the lorazepam intensol is mixed with water it stays a solution. I would hope that they know what they are talking about and how their meds work, but who knows.....

[[po...]]

gray cloud, it was a good idea to call West-Ward. However, I am not sure who answered: did you have a pharmacist on the line? The answer you received is not correct. Once the Intensol is mixed with water, the mixture is a suspension because lorazepam is insoluble in water (like other benzodiazepines). Also, even if the suspension seems clear to the naked eye, you would not be able to see the lorazepam crystals inside it if lorazepam were to precipitate (they are too small). This would require a microscope.

 

In fact, lorazepam is so insoluble in water that in bags used for intravenous administration, high and often toxic amounts of propylene glycol (69 grams per bag) are required as a solvent. IV administration of lorazepam thus require medical monitoring for a variety of adverse effects associated with the use of such a high dose of PG, especially for prolonged treatment.

[[Gu...]]

Hi!

 

I am 4 1/2 months off, and used to titrate utilizing a milk suspension.  Just wanted to report that I was in the habit of rinsing my syringes with distilled water, followed up by flushing them with water, and never had a problem with getting an infection from them, even after 2 1/2 years of tapering! Typically, the syringes would break after a few weeks of use, so I never had a problem with them getting too old.  I hope this helps!

[[po...]]

Thank you for your feedback, GumbyGirl! Just a clarification — when you say that you flushed the syringe with water after rinsing it, do you mean you poured water both inside (with the plunger removed) and outside?

[[gr...]]

So basically Potatosuer you are saying that even people that have dissolved their benzo in alcohol are not creating a true  solution even though the benzo was dissolved in alcohol and then  water was later added to the mix.  But Milk will create a true solution..... And basically you are saying that Lorazepam intensol, which is made by dissolving lorazepam in polyethylene glycol and propylene glycol no longer stays in solution when water is added, even though propylene glycol and polyethylene glycol mix and blend completely with water. I am not so sure about the milk thing...  There are many people here that seem to have created a solution by dissolving their benzo in alcohol or PG and have successfully taper off the benzo. And many people that have used the liquid form of benzo diluted in water have tapered off successfully. 

[[po...]]

gray cloud, please allow me to break your message down and respond point by point.

 

So basically Potatosuer you are saying that even people that have dissolved their benzo in alcohol are not creating a true  solution even though the benzo was dissolved in alcohol and then  water was later added to the mix.  But Milk will create a true solution.....

 

I would first like to clarify two points:

 

1) I have not mentioned alcohol (ethanol) as a solvent in this topic. It should be noted, though, that lorazepam is much less soluble in pure ethanol than diazepam; at a temperature of 30C, the latter is 3.3-fold more soluble in ethanol than the former (0.63 mg/mL vs 2.14 mg/mL) [1].

 

Further, BB members typically dilute their benzodiazepine in vodka (40% ethanol by volume), which solubilizes only 0.10mg lorazepam per 1mL at a temperature of 30C. [1] Assuming the lorazepam prescription solution is dosed at 2 mg/mL, a 10-fold dilution (i.e. adding 19mL vodka) would barely manage to keep the lorazepam dissolved; a 50 or 100-fold dilution is preferable, but this requires a whopping 99 to 199mL vodka and so is simply unsafe and impractical for tapering.

 

I invite you to read about the importance of having a sufficient “solubility sink factor” in my other thread to understand why a 50 or 100-fold dilution is preferable.

 

2) I have not stated that whole milk is a suitable solvent for lorazepam. I only know that it is one for diazepam, at a temperature between 25-40C, [2] but I do not know if that is the case for lorazepam since I have not researched the latter.

 

And basically you are saying that Lorazepam intensol, which is made by dissolving lorazepam in polyethylene glycol and propylene glycol no longer stays in solution when water is added, even though propylene glycol and polyethylene glycol mix and blend completely with water. I am not so sure about the milk thing...  There are many people here that seem to have created a solution by dissolving their benzo in alcohol or PG and have successfully taper off the benzo.

 

The key point that you are missing is the concentration of each solvent in either the oral prescription solution or the diluted mixture.

 

The oral prescription solution is highly concentrated in solvents. For instance, let’s suppose that a 1 mg/mL diazepam oral solution contains 40% ethanol by volume (i.e. 0.4mL ethanol per 1mL solution, as is the case for my own oral prescription solution) and that the remaining 60% is water. 1mL of this liquid can solubilize up to 1.90mg diazepam at a temperature of 25C. [3] Here, the high concentration in ethanol is what allows the benzodiazepine to remain dissolved. (As you know, this is a simplification; the addition of other solvents than ethanol at sufficient concentrations, such as propylene glycol and polyethylene glycol, enhances the solubility of diazepam in the liquid.)

 

However, diluting the solution with water reduces the relative concentrations of the solvents down to essentially nil. In my example, if I were to dilute my solution 10-fold, I would add 9mL water to 1mL solution, for a total of 10mL diluted mixture. This mixture would contain the 0.4mL ethanol from the solution, so it would be 4% ethanol by volume (compared to 40% in the solution). This is too low of a concentration to solubilize the diazepam in the mixture: 1mL solubilizes about 0.07mg diazepam, so the entire 10mL mixture can solubilize at most 0.7mg diazepam [1], whereas it contains 1mg diazepam. Thus, the result is not a solution but a suspension.

 

The same goes for other solvents such as propylene glycol and polyethylene glycol — their concentration in the mixture becomes too low to preserve a solution, too, so the benzodiazepine is likely to precipitate.

 

And many people that have used the liquid form of benzo diluted in water have tapered off successfully.

 

Once again, I would like to reiterate that I am not denying that people have had success with tapering by diluting their oral prescription solutions with water. I am only pointing out that it may carry the risk of uneven dosage reductions because of precipitation, and I believe BB members should be informed of this risk.

 

I hope that this clarifies my previous replies. Please let me know if there is something that needs more explanation.

 

[1] Jouyban, A., Shokri, J., Barzegar-Jalali, M., Hassanzadeh, D., Acree Jr, W. E., Ghafourian, T., & Nokhodchi, A. (2009). Solubility of chlordiazepoxide, diazepam, and lorazepam in ethanol+ water mixtures at 303.2 K. Journal of Chemical & Engineering Data, 54(7), 2142-2145. https://doi.org/10.1021/je900200k

 

[2] Macheras, P. E., Koupparis, M. A., & Antimisiaris, S. G. (1990). Drug binding and solubility in milk. Pharmaceutical research, 7(5), 537–541. https://doi.org/10.1023/a:1015881103340

 

[3] Shayanfar, A., Fakhree, M. A., Acree Jr, W. E., & Jouyban, A. (2009). Solubility of lamotrigine, diazepam, and clonazepam in ethanol+ water mixtures at 298.15 K. Journal of Chemical & Engineering Data, 54(3), 1107-1109. https://doi.org/10.1021/je8007827

 

[[gr...]]

I understand perfectly what you are saying, but it is not fact that the med precipitates out of solution. I have not seen that in my solution. My body is extremely sensitive to any changes. I get bad withdrawals with the slightest reduction in dose. If my solution was precipitating I would feel it immediately, which is not the case.

[[gr...]]

And it is also fact that Milk does not necessarily create a solution, more likely just a suspension as stated on the Benzodiazipine coalition website.

[[po...]]

It would be helpful that you provide peer-reviewed evidence from the literature to support your statements, gray cloud. As you may have noted, to the best of my ability, my statements are based on evidence from the literature; we cannot know what is fact or not unless it has been properly studied.

 

The evidence provided in my previous replies suggests that precipitation may occur because your water-solution mixture is supersaturated with lorazepam. If there is evidence in the literature that suggests otherwise, I would be happy to look at it and update my conclusions based on it.

 

Edit: one study has shown that when preparing a lorazepam infusion by diluting a commercial 4 mg/mL IV solution with an aqueous 5% glucose solution, “lower concentrations tend to be unstable and crystallization is likely to occur” — specifically when it is diluted to 2.3 mg/mL and below, and especially at and below 0.2 mg/mL (at a temperature of 18C) —. It also shows that the lower the temperature the infusion is prepared at, the more likely it is to crystallize, [1] so refrigerating a batch of diluted mixture is a problematic practice if it is not brought out of the fridge and up to ambient temperature before dosing. Unfortunately, this may in turn affect the stability (“shelf life”) of the diluted mixture.

 

Importantly, it should be noted that crystallization happens in spite of the high concentrations of propylene glycol and polyethylene glycol present in the IV solution (which diminish the more diluted the solution is), so this suggests precipitation is especially likely to happen when diluting an oral prescription solution with water.

 

[1] Vellema, J., Hunfeld, N. G. M., Van den Akker, H. E. A., & Ter Horst, J. H. (2011). Avoiding crystallization of lorazepam during infusion. European journal of pharmaceutical sciences, 44(5), 621-626. https://doi.org/10.1016/j.ejps.2011.10.010

[[po...]]

And it is also fact that Milk does not necessarily create a solution, more likely just a suspension as stated on the Benzodiazipine coalition website.

 

The Benzodiazepine Information Coalition’s website states:

 

In the liquid titration approach, a pill is either crushed or allowed to disintegrate in a premeasured (in milliliters) amount of milk or water to create a suspension.

 

In our case, we are not using pills but an oral prescription solution. Diazepam is sufficiently soluble in milk at temperatures between 25-40C, so the diluted mixture remains a solution. [1] As I stated previously, I have not said that this is the case with lorazepam because the lack of relevant literature precludes from knowing whether this is also true for lorazepam.

 

I would also like to note that the BIC’s website is erroneous regarding the “safe” dilution of an oral prescription dilution in water, specifically because of the poor solubility of benzodiazepines in water.

 

[1] Macheras, P. E., Koupparis, M. A., & Antimisiaris, S. G. (1990). Drug binding and solubility in milk. Pharmaceutical research, 7(5), 537–541. https://doi.org/10.1023/a:1015881103340

[[gr...]]

https://doi.org/10.1016/j.ejps.2011.10.010  This states that crystallization of lorazepam during infusion occurs because glucose is an anti-solvent.

Is  propylene glycol and polyethylene glycol both glucose?  cannot find info. on this...  They had mixed the lorazepam solution with a water and glucose solution which were both in the I.V.  The glucose acts as an anti solvent, so without glucose it does not crystalize. I do not believe that their is glucose in the lorazepam intensol..

[[po...]]

Water is an anti-solvent too, for benzodiazepines. The conclusions of the article apply even if only an aqueous solution without glucose is used.

 

Propylene glycol and polyethylene glycol are both glycols, which are diols; they are unrelated to glucose, which is a carbohydrate. https://en.wikipedia.org/wiki/Diol

[[gr...]]

LOL That is not the conclusion of the article.  That is YOUR conclusion of the article. No where in the article did it state that water was the problem. and reducing water was not the solution but reducing the glucose was. Or reducing the strength of the lorazepam solution...

[[po...]]

LOL That is not the conclusion of the article.  That is YOUR conclusion of the article. No where in the article did it state that water was the problem. and reducing water was not the solution but reducing the glucose was. Or reducing the strength of the lorazepam solution...

The conclusion comes from corroborating the evidence in this article with the following evidence:

 

- Jouyban’s research, cited and explained in my previous replies, on the solubility of lorazepam in water and propylene glycol mixtures (including water only)

 

- the monograph for lorazepam injections stating that lorazepam is “almost insoluble in water” in the Description section (i.e. water is an anti-solvant for lorazepam): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4084fa74-9fd2-45ef-9d56-27bfa31d4e46

 

- two articles on the issues with diluting diazepam, similarly to lorazepam, no matter (1) the solution used for dilution (sterile water for injection, saline or an aqueous glucose solution), (2) the dilution ratio. [1, 2]

 

[1] Onuki, Y., Hasegawa, N., Kida, C. et al. Supersaturated state of diazepam injection following dilution with infusion fluid. J Pharm Health Care Sci 1, 9 (2015). https://doi.org/10.1186/s40780-014-0009-9

 

[2] Newton, D. W., Driscoll, D. F., Goudreau, J. L., & Ratanamaneichatara, S. (1981). Solubility characteristics of diazepam in aqueous admixture solutions: theory and practice. American journal of hospital pharmacy, 38(2), 179–182. https://doi.org/10.1093/ajhp/38.2.179

[[gr...]]

Well for some odd reason it is working for me. I have not had any problem with it precipitating. So I am not very concerned about it.

It has been nice talking to you, but it is time for me to get to other things. You take care and good luck with your taper.... Hope you start feeling better soon and can get on with your life!!!

[[po...]]

I hope that your liquid titration will guide you more gently through the rest of your taper, gray cloud. As I have been learning, liquid formulations of benzodiazepines — and, in general, formulations of medication — are difficult and tricky to design. There are many variables to control to ensure that a formulation remains stable (no degradation, including precipitation) and potent over time; it suffices to read a research article on developing a formulation to realize the complexity of the matter.

 

Unfortunately, many of us do not have access to a compounding pharmacy that could provide a more reliable solution or suspension than the homebrew liquids we prepare on our own. We are also left to deal with the issues that arise from it, and sometimes they may be subtle. For example, crystallization may be partial only and invisible to the naked eye, or our batches may lose potency over a few hours or days unbeknownst to us. There are no readily available indicators (to us laypersons) to spot such issues. Researching the physical and chemical properties of benzodiazepine liquid formulations helps with trying to mitigate these risks that eventually result in dosage errors; in a way, one could see it as damage control.

 

These issues may feel exaggerated to people who have been doing, or have done, a liquid titration with potentially unsafe methods successfully, and I understand why that is so — “don’t fix it if it ain’t broken”, as the saying goes —. The point is certainly not to blame or to cross anyone (we all are doing our best trying to taper with our limited knowledge and equipment and with the impairments we face), but to promote harm reduction through safer and, importantly, practical methods that we can hopefully glean from the evidence available in the literature.

 

Yes, it may seem from the outside that those of us who are discussing the technicalities of liquid formulations are nerding out We are scientifically curious, of course, but beyond that, harm reduction is an important matter that needs to be dealt with — every BB member knows how badly benzodiazepines can mess us up —.

[[po...]]

Regarding cleaning my syringes, I purchased a few 100mL squeeze bottles with small openings and put distilled water inside one of them and 90% modified alcohol (ethanol, isopropyl alcohol and acetone) in another one. I rinse the syringes with distilled water first, then with alcohol, and let them air dry afterwards. Having cleaned them up a few times now, they remain easy to manipulate. The alcohol doesn’t seem to be making the plunger stick to the body of the syringe. I can do this in my bed without making a mess (any drop of distilled water or alcohol that spills onto my mattress evaporates quickly anyway), so this works well for me.

 

However, I cannot rule out that the alcohol doesn’t affect the integrity of the syringe and, in turn, its accuracy. It stays in the syringe for about 30 seconds, the time that I need to swish it around, which is not long, but deterioration may build up over the course of several cleanings.

 

For illustration, here are the squeeze bottles: https://www.amazon.de/Octopus-Plastic-Squeeze-Laboratory-Garnish/dp/B076ZQMSXW/

[[po...]]

I found the CDC’s recommendation for cleaning syringes — I should have checked official sources first. They do not recommend alcohol, but pure bleach; first rinse with water for 30 seconds, then with bleach for 30 seconds, and lastly with water again for 30 seconds. https://www.cdc.gov/hiv/pdf/library/pocket-guides/cdc-hiv-syringe-service-pocket-guide.pdf

 

This guide is aimed at people who inject with needles for the prevention of viral infections. Bleach might be over the top for UHT milk that has been stored in the fridge, but it doesn’t change anything to my procedure (except for rinsing one last time with water), so I will probably replace the modified alcohol with bleach.