Adsorption? Check my science!

[ayjay]

A few years ago I helped put together a pamphlet on preparing MS Contin for injection. This method is intended as a "next best" if micron filters are not available. I can't post the whole pamphlet - so here's most of the text without pictures:

Use a swab to wipe off the coloured coating on the tablet. Wait for the tablet to dry out.
Put the tablet in the bowl (or large spoon) and crush into a fine powder with the teaspoon.
Add 3ml of water to the powdered tablet. Grind up the water and powdered tablet with the teaspoon. Keep going until you get a smooth, milky liquid.
Drop about half a cotton ball into the liquid. Just let it sit there and absorb the liquid. Wait. The longer you wait, the better the result.
Place the 3ml barrel on the top of the cotton ball. Don’t push it right into the cotton ball, or you will suck up the wax. Draw back the plunger. You should end up with about 2.5ml of clear liquid. This is morphine sulphate in solution.

Am I right in thinking that adsorption of the microcrystalline cellulose ("wax") onto the cotton wool is what has taken place? The method seems to work, and better than any other (apart from micron filters of course). There will still be some talc in solution, which is not great, but this method seems to give the best "drugs to crap" ratio.

A second question then - is there any commonly available material that could be used as an adsorbent to remove talc from a solution? Or maize starch?

This has become topical in recent weeks as we are experiencing a heroin shortage, which is driving up pill injecting - morphine and bupe in particular. We sell the micron filters, but cost is a barrier to consistent use. If we can offer people some alternatives, we may reduce injecting related harms. Just filtering through cotton wool is a poor last alternative (removes particles bigger than about 50microns, apparently. But capillaries can be as small as 2microns). Pill filters are very good but not funded so we have to sell them. I'm casting around for something in the middle...

 

[fastandbulbous]

Am I right in thinking that adsorption of the microcrystalline cellulose ("wax") onto the cotton wool is what has taken place?

Er, yes and no. The wax isn't microcrystalline cellulose, or any cellulose like polymer. The wax is due to the presence of long chain fatty acids (eg stearic acid); the cellulose type compounds are the ones responsible for increasing the viscosity of the soln made from the pills if boiling or nearly boiling water is used to prepare them. The cotton wool will prevent most of the wax from getting into the syringe, but nowhere near enough.

To get the best results, it's best to treat the pills with water at about 70'C (temp of a fairly hot cup of coffee/tea) for long enough to melt all of the wax present, then let the mixture cool as slowly as possible. This is because the slower it cools, the longer the droplets of molten wax have to come together and form larger droplets that eventually resolidify into large lumps of wax (better for removing with something like cotton wool). Rapid cooling produces lots of very small wax particles that had chance to pass through anything other than a micron filter. I did post a method a while back that's really efficient, but as it involves getting a solvent from a modelling shop, it's probably going to be used even less than micron filters.

To be honest, wax sustained release preparations that have only been through a cotton wool ball is really only suitable for plugging; using the soln obtained by that method for IV is just asking for the sort of vascular blockage that results in people losing hands, feet, legs, arms, their sight or even their lives. I don't know how much they sell for in the US, but as a fraction of the cost of their daily opiate intake, it'll be tiny. So if they're coming in for clean needles, begrudging a dollar for one after spending maybe $100-$200 on drugs almost makes me think I've got no sympathy for them if they lose an arm or a leg. It's not as if that single dollar means the difference between scoring or not...

 

[ayjay]

OK - so it's back to the drawing board. I checked my contin contents:

MS Contin
Composition Active. Morphine sulfate BP.
Inactive. Tablets. Lactose (5, 10, 15, 30, and 60 mg tablets only), hydroxyethylcellulose, cetostearyl alcohol, magnesium stearate and talc. All tablets are coated with hypromellose, macrogol 400 and titanium dioxide (E171). The coatings also contain: iron oxide red (E172) (10 mg tablet); iron oxide black (E172) (10 and 100 mg tablets); iron oxide yellow (E172) (10, 15 and 100 mg tablets); quinoline yellow (E104) (15, 60 and 200 mg tablets); patent blue V (E131) (15 and 200 mg tablets); indigo carmine (E132) (15, 30 and 100 mg tablets); erythrosine (E127) and sunset yellow FCF (E110) (30 and 60 mg tablets).

My understanding was that the hydroxyethyl cellulose was the slow release agent, but this is wrong? Hmmm.

I should clarify the method a bit - the cotton ball is rather larger than what one would use for filtering. For filtering, one would use a rolled up piece about the size of half a pea. In the method, about half a ball of cotton wool is dropped into 3ml of drug solution/excipient suspension. After a few minutes, the cotton wool has soaked up the whole lot and is completely sodden. A 3ml syringe (sans needle) is placed on the top of the cotton ball without pushing down. The drug solution is drawn off the top of the cotton ball. This final solution is slightly cloudy, so still contains some excipients. However, the cotton ball is slimy, with a neutral taste (indicating very little morphine present). Note that this method is not a filtering method. The cotton fibres are not being used as a sieve to remove particles; rather, the majority of the excipients are adhering to the surface of the cotton fibres (hence my suggestion of adsorption being the mechanism).

Commonly, people heat the crushed tablet with water while preparing for injection. As you point out - this can lead to a gluggy solution. I've had people ask for 23g needles because the resultant glug is too thick to pass through a thinner needle . Some people use a method where they have a filter (cotton wool or ciggy filter) sitting in chilled water. They add the chilled filter to the heated mix, causing the excipients to set around the filter, then draw up through the filter as usual. This method is OK (still not as good as a micron filter) - but a proportion of the morphine tends to get trapped in the congealed wax. The method I describe above seems to be more efficient.

As a health provider, I can't sit back and say "people should be able to find the extra $1.10 for filters - bad luck if they can't". I have to acknowledge the reality - for whatever reason, not everyone has the spare change for filters every time they inject pills. It is not as simple as saying "you had $100 for your drugs - why haven't you got $1.10 for a filter?" The way people who are opiate dependent operate within the illicit drug market is far more complex. I have to look for ways to reduce the harms associated with injecting practices because:
I'm a dedicated harm reductionist
It's my job
I have better access to ideas, knowledge and resources - I can make things happen that other people can't

So I'll clarify my original question. Any ideas about how tablet excipients in MS Contin and Subutex can be removed without micron filters, yet more efficiently than a simple cotton ball filtering?

 

[fastandbulbous]

Yes, it helps with the slow release by preventing the tablet from disintergrating as quickly (less surface area ), but the wax in that will mainly be the cetosteryl alcohol (a waxy solid at room temp with a low mp)

 

[Coolio]

Hydroxyethyl cellulose mixed with ethyl alcohol is what makes the inside of a Duragesic a thick gel.

 

[ayjay]

Thanks fastandbulbous. I tracked down your solvent extraction method ( http://www.bluelight.ru/vb/showthread.php?t=204877&highlight=extract*+contin+solvent ) - I notice that you still advise use of micron filter before injecting. Are you just being super cautious here? If there is still talc in your final product (magnesium silicate or similar?) then you would still have to use a micron filter. I guess it depends whether talc is soluble in toluene... In any case, as you say not suitable for my purposes.

Any physical chemistry heads out there? I'd like to get some support for the method I detailed above - something better than my guesswork anyway

 

[fastandbulbous]

The micron filter is for any nasty bacteria that might have got into the preparation (I do it as standard with everything). Using the method I outlined stops the micron filter from getting clogged with resolidifying wax etc

 

[raybeez]

You don't think the toluene/ethanol/isopropanol would take care of that? The latter two are used to clean injection sites prior to drug administration. If the powder is allowed to evaporate from solvent under sterile conditions, and redissolved in sterile water, it should be sterile.

The micron filter is for any nasty bacteria that might have got into the preparation (I do it as standard with everything). Using the method I outlined stops the micron filter from getting clogged with resolidifying wax etc

 

[BobbyTBobby]

Does anyone know how to maximize absorption under the tounge with Subutex?

 

[ayjay]

The micron filter is for any nasty bacteria that might have got into the preparation (I do it as standard with everything). Using the method I outlined stops the micron filter from getting clogged with resolidifying wax etc

That would only be a problem if the tablet was mixed with warm water. If cold water is used, a 0.8 or 0.44 micron filter works fine to remove excipients. You could filter again to remove bacteria - but my thinking to date has been that bacterial load is more significant when injecting diverted buprenorphine (ie - scooped out of the mouth when pharmacist not looking).

BobbyTBobby - the main problem with Subutex seems to be accidental swallowing of part of the dose. This is worse when tablets are crushed by dispenser. You can thus maximise sublingual absorption by avoiding crushing or breaking up the tablets...

 

[fastandbulbous]

You don't think the toluene/ethanol/isopropanol would take care of that? The latter two are used to clean injection sites prior to drug administration. If the powder is allowed to evaporate from solvent under sterile conditions, and redissolved in sterile water, it should be sterile.

After getting a septic abcess from a puncture wound cat scratch, I don't think there's such a thing as being too cautious when it comes to making up sterile solutions (years of IM use without a hitch, one cat scratch I forget to clean and I get a week in hospital, IV antibiotics and a manky big hole in my leg). There's a possibility of airbourne bacteria getting in during the transfer of the powder from the evaporating vessel to the one used to make the sterile soln.

As I said, take every precaution possible when making up a solution for injection; I even reheat the ketamine solution in the vial (with ext boiling water bath) if it was prepared more than a couple of hours previously.

 

[iisthejulie]

hey there , jus wondering , i have a mass ass question , i have been hearing about the new oxy contins comin ou t, im a fuckin tad confizzled... is it the ones that are called percocet?? the 3/325 ones that they are fuckin up or is it the 10 and 20's?? cause eaither way fuck that .. ive been hearing bad shit about them!...