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Hydromorphone solubility

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raybeez

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I've been trying to track down some information on hydromorphone solubility (specifically for the free alkaloid, but also for various salts), and I haven't had much success. The information is being sought for a theoretical a/b isolation of Hydromorphone HCl from pharmaceutical preparations. Here is what I've managed to find so far:

Hydromorphone (base):
- Properties: Crystals from ethanol, mp 266-267 [No solubility data provided!] (Merck Index 13th ed.)

Hydromorphone HCl:
- Properties: Crystals, dec 305-315° (evacuated tube). Sol in 3 parts water; sparingly sol in alc. (Merck Index 13th ed.)
- Solubility: Soluble 1:3 in water and 1:100 in alcohol (90% ); practically insoluble in chloroform and ether. (Purdue's hydromorphone physician monograph)

Does anybody have any additional solubility data, especially for the freebase form? Also interested in seeing pKa's for the compound to approximate pH required for conversion of salt to free base. Propositions for a theoretical a/b extraction would also be welcome.
 
I would assume that the freebase/base is very soluble in butyl/amyl alcohol as most alkaloids of this nature are... especially with it's oxidized 6-OH. I think the isoeletric point should stay close to morphine, but possibly just a bit higher because of the functional ether, which is now between the 4 and 5 position.
 
DrugPhreak said:
I would assume that the freebase/base is very soluble in butyl/amyl alcohol as most alkaloids of this nature are... especially with it's oxidized 6-OH. I think the isoeletric point should stay close to morphine, but possibly just a bit higher because of the functional ether, which is now between the 4 and 5 position.
Click to expand...

^^^ Thanks for the info. So how would you conceptially incorporate this into a theoretical a/b of hydromorphone HCl from an rx prep?

I just thought of something looking at the HCl's alcohol solubility. Could this not be exploited?

1) pulverize sufficient pills to yield 1g of hydromorphone hcl, add to hot (~75C) ddh2o, and magnetically stir for 0.5hr
2) rapidly vacuum filter while hot
3) Adjust the alcoholic content of the filtrate to 90% with anhydrous alcohol
4) Reduce the volume at a low heat to aprox 5mL, and place in an ice water bath. ~95% of the hydromorphone hcl should precipitate

Perhaps 10 or 20% etoh could be used in the first step to dissolve the pills, so less 100% etoh would be needed in step 3.

Thoughts?
 
^ What are the inactive ingredients in the pill? Hypromellose (hydroxypropyl methylcellulose) and povidone (which are often added to pills to prevent easy extraction) can be a real bitch to get rid of.
 
redeemer said:
^ What are the inactive ingredients in the pill? Hypromellose (hydroxypropyl methylcellulose) and povidone (which are often added to pills to prevent easy extraction) can be a real bitch to get rid of.
Click to expand...

^ I can't get a list of the inactive ingredients, but the theoretical pills in question are generic PMS-hydrocodone (Pharmacscience)
 
Well, this is how a friend of mine extracts codeine from codeine-containing pills:

1. Add pills and enough NaOH to freebase the codeine to a coffee grinder and grind to a very fine powder.
2. Slowly add anhydrous IPA to the powdered pill/NaOH, seeing to it that the mixture doesn't heat excessively, until the mixture forms a thin paste. Stir for a good 15 minutes to ensure complete conversion of the salt to its base.
3. Extract the paste three times with non-polar solvent to obtain codeine freebase.
 
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The Merck Index will give a full list.

It's worth considering that hydromorphone has a convenient ketone (=O) moiety which will form an insoluble bisulfite complex. See For those wishing a little more detail on what the bisulfite adduct looks like for an aldehyde, below is an excerpt from Introduction to Organic Chemistry by Fieser & Fieser, 1957, p. 158.

I don't know if the codeine thing will work as well with hydromorphone because it has a phenol & a ketone so the freebase is almost certain to have at least some water solubility.
 
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