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Valium 5mg titration - dry or liquid micro taper?


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Re: your concern about drug/water mixture remaining on the lid of the mixing/drinking container …

 

1. Prepare the drug/water mixture.

2. Remove XmLs of the mixture, drink the remaining YmLs.

3. Add some water to the container.

4. Replace the lid.

5. Swirl the water around the container and the inner surface of the lid.

6. Remove the lid.

7. Drink the rinse water.

 

Repeat Steps 3 - 7 one more time (or as many times as needed for you to feel confident you have removed and ingested any drug/water mixture remaining on the inner surfaces of the container and the lid).

Oh, I had not thought about rinsing the lid. Clever and simple solution. For the umpteenth time, thank you, Libertas — it is so useful to have your working brain helping my slow one. Much appreciated.

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Thank you, Libertas. I do feel better now that I am on day 7 of my updose to 7.5mg.

 

I am not sure that I have understood the measure/ingest method. When you say:

 

At that point, instead of measuring 25mL and discarding it, you could obtain the same dose by measuring 25mL and ingesting it. 

 

How do you mean that the 25mL should be measured, then? Should it be drawn from the 50mL of diluted solution in five such iterations: draw 5mL with the 5mL syringe and pour it directly from the syringe into my mouth? This seems laborious.

 

(If so, then this method is interesting in that it is equivalent to preparing two batches at once, as only at most half of it is consumed at once. I do not know if the remaining solution can be kept for the next day, though I presume that it should be possible if it is stored under the same conditions as the prescription oral solution (away from light in a dry room, etc)).

 

EDIT: Warning: if your oral prescription solution is at 10mg / mL, DO NOT prepare under 50mL of diluted solution when you taper below 5mg diazepam, as suggested in the following paragraph, to ensure sufficient measurement accuracy. See Libertas’ post: http://www.benzobuddies.org/forum/index.php?topic=267260.msg3369558#msg3369558

However, because of the tense situation with the supply of prescription oral solution in my country for the time being, I am planning to reduce the amount of diluted solution prepared as I taper down, in steps of 10mL. For instance, at 2.5mg diazepam, I would not prepare 50mL of diluted solution (5mg diazepam) but 30mL instead (3mg diazepam) and thus discard only 0.5mg diazepam rather than 2mg. This reduces waste so it helps a bottle of prescription oral solution last longer.

 

Being excessively cautious, I also prefer to measure the amount of distilled water with the graduated cylinder every day (i.e. every time I prepare a batch). This is of course much more laborious than using a pre-marked meniscus on the mixing/drinking container. I know that I could update the meniscus mark every time I decrement by 10mL, but again, I would like to be precise.

 

One aspect of decrementing the amount of diluted solution I prepare in steps of 10mL that is less laborious than the measure/ingest method is that I have to use the 5mL syringe at most twice. Indeed, I need to remove at most 9mL (for instance if I wanted 4.1mg diazepam instead of 5mg.). In comparison, I would have to use the 5mL syringe five times to remove 26mL.

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Unfortunately, the adapter caps that I have received do not fit my vial of Valium. Because of my cognitive impairment, I don’t want to use the drop adapter as I will lose my focus while I count the drops and miscount.

 

I have thought of a simpler protocol to dilute the entire 20mL vial from 1% (10mg / mL) to 0.1% (1mg / mL) by adding 180mL distilled water. This only needs to be repeated once every few weeks.

 

Warning: DO NOT follow this protocol, see Libertas’ post below — the diluted solution cannot be kept for longer than a few days.

 

Equipment:

- 100mL graduated cylinder

- 8oz low profile mason jar with a wide mouth (to facilitate drawing from it with a syringe)

- Deionized or distilled water

- 10mL syringe

- 1mL syringe

- Brush to wash the graduated cylinder

- Drying rack for the graduated cylinder (DYI)

- Optional: acetone or alcohol

 

Note: I do not have a 200mL or 250mL graduated cylinder so I am using a 100mL graduated cylinder here (tolerance +/- 0.5mL).

 

Cleaning the equipment:

 

1. Wash the mason jar and the graduated cylinder with warm tap water and soap or detergent. Use the brush to clean the inside of the cylinder without scraping it against the glass.

2. Rinse the inside and the outside of the mason jar and of the graduated cylinder with distilled water 3 to 4 times (to avoid residues from forming when drying).

3. (Optional.) To speed air drying, rinse the mason jar and the graduated cylinder with acetone or alcohol.

4. Hang the graduated cylinder upside down (by the base) on the drying rack.

5. Allow the mason jar and the graduated cylinder to air dry completely.

 

Sources:

- https://www.txstate.edu/chemistry/student-resources/Stockroom/cleaning-laboratory-glassware.html

- https://www.sigmaaldrich.com/EN/us/technical-documents/protocol/chemistry-and-synthesis/reaction-design-and-optimization/cleaning-glassware

 

Diluting the solution of Valium:

 

1. Measure 100mL distilled water with the graduated cylinder.

2. Pour the distilled water in the mason jar.

3. Measure 80mL distilled water.

4. Pour 60mL distilled water into the mason jar.

5. Pour the entire 20mL vial of Valium into the jar.

6. Rinse the vial:

- 6.1: Carefully pour 10mL distilled water into the vial.

- 6.2: Close the vial with its (leakproof) lid and shake.

- 6.3: Pour the content of the vial into the mason jar.

- 6.4: Repeat steps 6.1 to 6.3 once (i.e. with the remaining 10mL water).

7. Close the mason jar with its leakproof lid and shake.

8. Wait a few seconds, open the lid, tap it lightly vertically against the mason jar so that the remaining liquid on the underside falls into the jar.

 

Measure/ingest method, with an example of 7.5mg diazepam:

 

1. Repeat steps 7 and 8 above.

2. Measure 7mL diluted solution with a 10mL syringe, ingest.

3. Measure 0.5mL diluted solution with a 1mL syringe, ingest.

 

Finally, to taper by decrements of 0.1mg, simply draw 0.1mL less than the previous amount of diluted solution. (One can even decrement by smaller steps, depending on the graduations of their 1mL syringes.)

 

Of course, the mason jar needs to be stored away from light as it is not amber colored. One should ideally use a 8oz amber glass bottle with a fitting adapter cap for syringes.

 

As with the previous protocol, one issue is that it becomes a bit difficult to draw the last few milliliters of diluted solution from the mason jar with a syringe. (Tilting it slightly in a secure way helps, though.)

 

Other than that, is there anything wrong with this protocol?

 

(Side note: the graduated cylinder could even be replaced by a 0.01g precision scale. These scales usually have a weight limit, so one would need to use a lightweight beaker or a spouted cup, but they can measure the 180mL distilled water fairly accurately.)

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Agh, I was not aware of this but it makes sense. Thank you Libertas. I won’t risk it, then. I will count the droplets as carefully as I can instead.

 

It is annoying that using oral syringes for medication is not a common practice in my (European) country as it is in the US. Non-intravenous medication here comes either in pills, vials with droplet adapters, or vials with caps for needle syringes (intramuscular injections).

 

Adapter caps seem to be made only in the US so it can’t be known in advance whether they will fit a certain European vial, even when having the measurements of the vial mouth and of the adapter cap. It is a trial and error process. (Also, only one small company in my country imports adapter caps from the brand Health Care Logistics.)

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Thank you for these ideas. I might transfer the solution to a smaller syringe-friendly glass recipient and keep it away from light, that seems to be the easiest solution for me.

 

For future readers, I have edited my previous post to mention your warning about the shelf life of the diluted solution.

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Well, I have trained myself to use a 1mL syringe by drawing too much water and pressing to draw it out. It takes some fine thumb control to slowly glide the plunger down 0.01mL by 0.01mL! I’ll continue training until I master this skill. I also need to train myself to draw just the right amount.

 

Edit: drawing/pulling is much easier than pressing the excess solution out.

 

Libertas, given that my 1mL syringes have 0.01mL graduations, may I ask why I cannot draw directly the amount required from the vial (e.g. 7.3mg would be 0.73mL)? Are the graduations too unreliable/inaccurate? They are tuberculin syringes without needles (Nipro brand).

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Thank you for providing me these informative resources. I suspected such shenanigans. The part on the tolerance stack is interesting and was one of my concerns.

 

The loss of accuracy as the volume measured goes down in a 1mL syringe is much more significant than I expected. I understand from the article that it is preferable to measure 0.5mL or above to remain in a +/- 5% accuracy range instead of falling down to +/- 10% (or +/- 16% under 0.1mL). So I will always have to draw at least 0.5mL from the vial (0.5mg diazepam) — i.e. prepare at least 50mL of diluted solution — to ensure acceptable accuracy.

 

That said, despite the ISO norm for syringes, I suppose the accuracy range does not suddenly jump from +/- 5% at 0.5mL and above to +/- 10% under 0.5mL — it should be more like a gradient? That would mean we are probably close to +/- 10% accuracy at 0.5mL. This is making me wonder about the accuracy of the droplet adapter supplied by the manufacturer, too.

 

I also realize now that when preparing between 51mL and 89mL of diluted solution, the +/- 10% accuracy range of the 1mL syringe accuracy between 0.1 and 0.5mL will interfere with the measurement of the distilled water. For instance, to prepare 75mL, I need to draw 0.25mL distilled water so I would be drawing anywhere between 0.22 to 0.28mL water due to the error of ~0.03mL (rounded up to keep two significant numbers). This is fairly minimal and falls well within the +/- 0.5mL tolerance of the 100mL graduated cylinder (which is an order of magnitude greater). Is this a concern?

 

Anyhow, I think my prescriber should agree to prescribing me 5mg diazepam (15 drops) even as I reduce my dose below 5mg, so I won’t run out because I have to prepare solution in excess then. I just have to hope there won’t be more shortages of the oral prescription solution coming because of the manufacturer.

 

Edit: I have added a warning to one of my previous posts to reflect this information. http://www.benzobuddies.org/forum/index.php?topic=267260.msg3368491#msg3368491

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  • 2 weeks later...
If the diluted solution is prepared in advance the same day, how long can it be stored out of the fridge, if at all? Would anywhere between 1 to 6 hour(s) be OK, or is it too risky?
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Noted, thank you. Here is what the leaflet specifies (bolding mine):

 

“5. HOW TO USE VALIUM 1 PER CENT, Oral Solution in drops?

 

Keep this medication out of the sight and reach of children.

 

Do not use this medication after the expiration date indicated on the bottle after EXP. The expiration date refers to the last day of that month.

 

No special storage precautions.

 

Do not dispose of any medication down the drain or with your regular garbage. Ask your pharmacist to dispose of medications you no longer use. This will help protect the environment.”

 

https://base-donnees-publique.medicaments.gouv.fr/affichageDoc.php?specid=63196256&typedoc=N

 

I suppose I can give it a try. It is more manageable for me to be able to dilute the solution ahead of time, so that I can break down that task step by step to pace myself (due to my chronic illness).

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I prepared it 2h30 or 3h ahead of time yesterday and it went fine. No precipitate or other physical change, no change in effectiveness that I could discern. That’s helpful!
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I have read pages 1-3 of this thread, and skimmed pages 4-5. You may or may not be planning on maintaining diazepam solubility with this formulation. I hope that you are not making that as an assumption. This post mainly concerns solubility concerns for diazepam aqueous solutions.

 

TL;DR

In my opinion, aqueous diazepam SOLUTIONS (almost entirely water based) are not practical. Aqueous diazepam SUSPENSIONS are what you should assume you have in this case, unless your formula has a significant amount of a better solvent for diazepam (like ethanol). Suspensions have their own challenges and problems. Use credible literature preps if they exist. If they don't, new formulations are always a risk despite what you think should be possible. Just know that going in.

 

Full:

I want to make it clear for future readers that the MAXIMUM amount of diazepam that will remain dissolved in 100 mL of water, at equilibrium, is 7 mg (see PubChem references below). The "working" solubility (my own term for this post) is significantly less than that. You would never want to rely on a drug remaining dissolved when it is at the precipice of crystallizing. That is where you would be if you actually get 7 mg diazepam to fully dissolve in 100 mg.

 

Crystallization is very unpredictable, and can occur due to many factors, including temperature fluctuations, a seeding crystal or a speck of dust, a scratch in your glassware, etc. You need a significant buffer zone in what you expect to stay dissolved if keeping the diazepam dissolved is truly your purpose. In pharma, the minimum standard for having sink conditions is a factor of 3-5, but even better to have a factor of 10 or more. So divide 7 mg by 3 or 5, and you have a "working" solubility closer to 1-2 mg diazepam per 100 mL of water at 25 C. This is just one reason why I believe diazepam aqueous SOLUTIONS are not practical for a diazepam taper - too much water, and not enough control over precipitation! If your goal is to make a diazepam SUSPENSION, then solubility isn't the primary concern anymore.

 

Suspensions can also be difficult to control and maintain. They have their own set of distinct challenges, including agglomeration, and less than ideal settling rates (which would be the case for water based solutions) which affects dosing. Much better to use credible literature sources for any sort of solution or suspension preparation, if at all possible.

 

 

Water Solubility of Diazepam:

retrieved from https://pubchem.ncbi.nlm.nih.gov/compound/Diazepam#section=Solubility

 

-In water, 66 mg/L at 25 °C

Yalkowsky, S.H., He, Yan., Handbook of Aqueous Solubility Data: An Extensive Compilation of Aqueous Solubility Data for Organic Compounds Extracted from the AQUASOL DATABASE. CRC Press LLC, Boca Raton, FL. 2003., p. 1031

 

-50 mg/L (at 25 °C)

YALKOWSKY,SH & DANNENFELSER,RM (1992)

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I read how it is being done, and that it's being done this way bc 2 mg pills were not available, and less conc. commercial solution is also unavailable. I am primarily warning future readers that may hope to build upon this method as a precendent.
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Oh no, this is bad news… Thank you for this information, Nogoldchain.

 

Should I dilute the oral prescription solution with a solvent like PG instead of water, then? According to PubChem:

 

“ Sparingly soluble in propylene glycol; approx 62.5 mg/mL alcohol at 25 °C

 

McEvoy, G.K. (ed.). American Hospital Formulary Service-Drug Information 19 98. Bethesda, MD: American Society of Health-System Pharmacists, Inc. 1998 (Plus Supplements)., p. 1944”

 

Or am I better of switching to a dry micro taper with a good quality milligram precision scale? Did you use this one? https://www.amazon.com/American-Weigh-GEMINI-20-Portable-MilliGram/dp/B0012TDNAM/

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OK. I’ve ordered this milligram scale from a reputable German brand (Kern TGD 50-3CS05): https://www.kern-sohn.com/cgi-bin/cosmoshop/lshop.cgi?action=showdetail&ls=en&rubnum=produkte.221.222&artnum=TGD|-|-|222

 

I will try to hunt pharmacies for 2mg pills. The national drug regulator in my country does not list the 2mg pills as out of stock (the manufacturer has to inform them when this is the case — this is currently the case for the oral prescription solution). This means I should be able to find them somewhere.

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potatosaur, I don't know want you to have to throw away all the work especially you and Libertas have done here. I am not 100% sure of all the details of the current method you two have worked out. I know it has changed through the course of the thread to improve it. If this is working for you, that sounds like a good sign that you could be getting consistent doses day to day. If you are regarding all water diluted diazepam preparations from your 10 mg/mL diazepam stock as if they have turned into suspensions (as in, making sure well dispersed prior to taking aliquots), you may have nothing to worry about here. I don't know if that is the case or not.

If you are not mixing just prior to taking out aliquots, maybe you could consider making that change in some fashion? If you want, I can look into the propylene glycol for you. I know the ingredient well, but would want to see what is in the literature in terms of stability with diazepam before making any kind of statement. But if you want to keep on with this current method, I would support you if you have at least visual evidence that it is either a clear solution or a well dispersed suspension before removing aliquots for dumping or ingesting.

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I replied too soon, you have a new scale on the way. If you go the pill way, I guess that would change everything. If you cannot get pills, it is entirely possible to weigh each dose of the conc. diazepam solution you already have .

 

One possible alternative is to dose your 10 mg/mL solution, without dilution, by weight. Instead of using the graduated markings for volume on your dosing syringe or pipette. For this, you need to know the density of your 10 mg/mL solution. Once you ascertain the density by whatever means necessary (hopefully in the package insert but probably not), you could weigh the liquid into a lightweight receptacle that fits onto your balance. You consume in it's entirety, however it is you achieve that.

 

You will probably know the strengths and limitations of your balance better than I. On the positive side, it will be about the same weight per dose if you were weighing 2 mg pills. My 2 mg pills are about 175 mg each. And your 7.5 mg dose in liquid form should weigh in the ballpark of 750 mg.

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