Author Topic: Valium 5mg titration - dry or liquid micro taper?  (Read 3288 times)

[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #40 on: May 08, 2022, 12:15:01 am »
Does the drug information pamphlet that came with your medication include instructions for storage and/or proper use?

If not, then you may have to play this one by ear. (To my knowledge, you are the first member weve had who is using the highly concentrated solution available in your country.)

My guess (and its just a guess) is that it would be ok to keep the diluted liquid for 1-6 hours at room temperature, assuming that you (a) do not observe any physical changes in it (e.g. the formation of a precipitate) and/or (b) experience a change in effectiveness.
« Last Edit: May 08, 2022, 12:56:05 am by [Buddie] »
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[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #41 on: May 08, 2022, 06:30:18 am »
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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[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #42 on: May 09, 2022, 07:37:49 am »
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. Thats helpful!
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[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #43 on: May 09, 2022, 12:46:16 pm »
Thank you for the good news update, [...]!
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #44 on: May 09, 2022, 04:43:46 pm »
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)
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #45 on: May 09, 2022, 05:09:31 pm »
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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[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #46 on: May 09, 2022, 05:47:06 pm »
Oh no, this is bad news Thank you for this information, [...].

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/
« Last Edit: May 09, 2022, 06:35:31 pm by [Buddie] »
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #47 on: May 09, 2022, 07:02:00 pm »
OK. Ive 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.
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #48 on: May 09, 2022, 07:19:02 pm »
[...], I don't know want you to have to throw away all the work especially you and [...] 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.
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: Valium 5mg titration - dry or liquid micro taper?
« Reply #49 on: May 09, 2022, 07:39:04 pm »
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.
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.