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Liquid Preparation/Dosaging

Giza

Ex-Bluelighter
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If you had something with extreme potency, talking in the microgram range, wouldnt dissolving in liquid be the best bet for the most accurate dosing? If not, can somone explain why??

I.e. say you had something that the dose you wanted was 1mcg, and you wanted that dose dissolved in 1 CC (1ml) of liquid. So you took 1mg (1000mcg), and dissolved in 1000ml of liquid thus getting 1mcg/ml, and put it on a mag stirrer for a very very long time, like 10+ hours.

Wouldnt this be the absolute most accurate way? I remember somone saying no... I couldnt understand why. Anyone?

Is there any more accurate a way?
 
I can't see what's wrong with that method, but use a pipette and dilution measuring vessel (e.g. graduated cylinder) with reduced tolerances or error margins.
 
It also depends on where you got the drugs from. Unless the drugs were from an actual scientific supplier, you can't trust there weights.... but liquid is still the best mechanism.

It also depends on whether the drug is way soluble or not. If it's not soluble, it doesn't matter how long you stir it for.

Also measuring 1mL can be hard unless you've got a syringe or something.
 
Also depends on the stability of the drug. For example, we all know that chlorine and other nasties in tap water will destroy LSD molecules. Many compounds will be broken down by water itself. When we're talking micrograms, you don't have to destroy a whole lot of the compound before significant reduction of the potency of the solution has happened.
 
Understandable.

So lets say it had great solubility, and was stirred for sufficient timing and measured meticulously, it will mix evenly?

I dont understand physics or whatever is involved in this instance, but assuming everything dissolves, there will be X:Y 100% consistent ratio of BUFFER:ACTIVE??

Like it seems logically, there would always be pockets where thered be more buffer than other areas and vice versa, which in some instances could be lethal, but if the things dissolve fully, there is no chance of this?? Or is it just 'less' a chance than other methods?
 
Hmm lots of room for jibber-jabber here but the ball is in your hands wrt the arts and krafts of it all. Just wanted to point out that acid is very good preservative for storing these compound in an aqueous environent. Shoot for pH~4 and use citric acid for example.
 
Unfortunately the compound attemping to dissolve is very lipophilic and thus must be encapsulated inside hydroxypropyl beta cyclodextrin molecules to even get in an aqueous environment, which is not a problem and very cost efficient as so very little molecule is needed. But not sure how an acidic addition would be tolerated by the HPBCD/narcotic complex molecule? Doubt you have the answer either.

Question, in pharmaceutical IV preparations of injections, whats used to make it sterile? Benzyl alcohol? Any standard % of whats acceptable use?
 
Without knowing what the narcotic substance is it's hard to say whether stability of the complex would be compromised in a mildly acidic medium.

Here's some info on acid/base stabilization of hydroxypropyl beta cyclodextrin

Acid/Base Stability

Strong acids, such as hydrochloric or sulfuric acids, hydrolyze HPBCD. The rate of hydrolysis is dependent upon the temperature and concentration of the acid. The higher the temperature or concentration of the acid, the more rapid is the rate of hydrolysis. Weak acids, such as organic acids do not hydrolyze HPBCD

HPBCD is stable in bases. HPBCD is synthesized under basic conditions without opening of the BCD ring.

Within the commonly used range of pH for most products and processes, HPBCD is stable as shown in the table below

Stability of HPBCD from pH 4.0 to 9.0

Concentration HPBCD (ug/ml)

pH Initial Day5 % Hydrolysis
4.0 6.03 5.97 1.0
7.0 5.50 5.70 -3.6
9.0 5.20 5.10 1.9

HPBCD was incubated in buffers at 50'C for five days. The results indicated that little, if any hydrolysis occured.Variation in the assay could account for the differences found.


From here
 
Thanks. Thats a very comprehensive page.

Back to the original topic now, and this entropy, if say the task required suspending nanogram amounts, say 0.10mcg/ml, in large form like a gram @ a time, like I just cant visualise this in my head and its blocking me from understanding, wouldnt there be just way too many molecules of water verse molecules of the chemical to ever hope for some kind of even distribution throughout all the liquid? Maybe Im just visualising it all wrong, but a few nanograms of material cannot possibly (?) possess as many molecules as a ml of liquid could it? And therefore there will be areas in the liquid that would have more molecules than others and create blotches? Or is this a moot point, being that the molecules that are there, will be evenly distributed throughout all the molecules of water/acid environment via this entropy??
 
At certain times there will be microenvironments with slightly more molecules of drug that others... but on the whole, especially when the volume of the microenvironment increases, the amount of molecule will tend to the average.
 
Even with nanograms there are still quadzillions of molecules floating around. Sure, it's theoretically possible that they'll all bunch up in one corner of the bottle, but its also theoretically possible for all the air molecules in your house to bunch up in the bathroom, suffocating anyone in the other rooms!
 
Well it depends on what exactly that "something" is. Different chemicals have different stability rates. There are some synthetic drugs that have very weak molecular structures, therefor mixing it may result in a 'loss of potency' for that drug. And other chemicals may not even dissolve fully. Then you have a batch of liquid "something" with an uneven consistency.
 
There are some lypophilic drugs that have very poor solubility in aqueous media even at low pH. When doing acid/base extractions on such compounds you can forget about tossing the non-polar thinking that your alkaloid salt is going to behave 'normally' and reside in the aqueous layer like you would expect.
 
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