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Pharmacology - Dissolving benzos in Propylene Glycol for high BA in rectal use

Discussion in 'Benzodiazepines' started by seroquel, Sep 24, 2011.

  1. seroquel

    seroquel Newbie

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    31 y/o Female from Germany
    SWIM came to the decision to dissolve his benzos in Propylene Glycol for rectal usage. He made a fine powder out of lorazepam and diazepam. First he soaked the pills in approximately 1:1 water. then he airdryed the resulted paste for 24 hours. after that he crushed it to fine powder. what do think, in which ratio should i mix the powder and Propylene Glycol? i dont remember how many mg of the active substance the powder includes, because i used the powder every now and then... should i go just by volume for the mixing like 10 CC of powder mixed with 10 CC of Propylene Glycol. thanks
     
  2. Jatelka

    Jatelka Psychedelic Shepherdess Platinum Member & Advisor

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    Given that you don't know how many mg of product you have, how can you possibly expect us to give you dosage advice? To do so would go against all harm reduction principles
     
  3. seroquel

    seroquel Newbie

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    Re: Dissolving benzos in Propylen Glycol for high BA in rectal use

    hi, well, i had 15 x 5 mg diazepam pills and made the powder out of it. so that would be 75 mg in powder. i allready used some of it so i guess its about 54 mg powder left. and from what i understand when dissolving its not about the mg of the active substance, its about mass volume of the pills. of course its good to know how many mg the powder/pills have so you know your dosage afterwards. ok lets put it this way: i have 15 x 5 mg diazepam pills and want them to dissolve in Propylen Glycol for rectal use. how many ml of Propylen Glycol should be used for this? or for example is it possible to dissolve also some pills have the same size (mass volume) and maybe the same weight but one pill has 1 mg active substance and the other pill 10 mg. so you couldn't just say:"the ratio must be 1mg/1ml..." you know what i mean, the ratio should relate more to the weight of the pills?! thanks

    seroquel added 6 Minutes and 28 Seconds later...

    ########################################### Please forget the post above, it has errors.! ########################################### hi, well, i had 15 x 5 mg diazepam pills and made the powder out of it. so that would be 75 mg in powder. i allready used some of it so i guess its about 54 mg powder left. and from what i understand when dissolving its not about the mg of the active substance, its about mass volume of the pills. of course its good to know how many mg the powder/pills have so you know your dosage afterwards. ok lets put it this way: i have 15 x 5 mg diazepam pills and want them to dissolve in Propylen Glycol for rectal use. how many ml of Propylen Glycol should be used for this? or for example is it possible to dissolve to much like the active substance? also some pills have the same size (mass volume) and maybe the same weight but one pill has 1 mg active substance and the other pill 10 mg. so you couldn't just say:"the ratio must be 1mg/1ml..." you know what i mean, the ratio should relate more to the weight of the pills?! thanks

    seroquel added 0 Minutes and 16 Seconds later...

    ########################################### Please forget the post above, it has errors.! ########################################### hi, well, i had 15 x 5 mg diazepam pills and made the powder out of it. so that would be 75 mg in powder. i allready used some of it so i guess its about 54 mg powder left. and from what i understand when dissolving its not about the mg of the active substance, its about mass volume of the pills. of course its good to know how many mg the powder/pills have so you know your dosage afterwards. ok lets put it this way: i have 15 x 5 mg diazepam pills and want them to dissolve in Propylen Glycol for rectal use. how many ml of Propylen Glycol should be used for this? or for example is it possible to dissolve to much like the active substance? also some pills have the same size (mass volume) and maybe the same weight but one pill has 1 mg active substance and the other pill 10 mg. so you couldn't just say:"the ratio must be 1mg/1ml..." you know what i mean, the ratio should relate more to the weight of the pills?! thanks
     
    Last edited: Sep 25, 2011
  4. Mindless

    Mindless Gold Member

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    Diazepam is soluble in alcohol, but I'm not sure if it's soluble in propylene glycol, although PG is a diol and can act like an alcohol. If an attempt were made to dissolve diazepam into PG, my guess is that it would only need enough to cover the crushed diazepam tablets.

    I understand that it can be fun to play with substances, but I'm not sure what the advantage is of preparing such a solution. I imagine it's pretty easy to add a few drops of water and make a paste runny enough to plug via a syringe. This would only take a few seconds. There is an additional advantage to preparing pills one at a time; it makes use safer, by enabling accurate dosage.

    I don't think the speed of onset would be improved by using a base of PG, nor would it make any more of the diazepam available.
     
    Last edited: Sep 25, 2011
  5. seroquel

    seroquel Newbie

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    hi,
    ok, the thing is, i read if you don't dissolve the benzo for example in PG it wouldn't get absorbed so good by the body.
    that means if you just plug it as a paste mixed from water, the Bio Availability is much worse than a PG solution.

    the thing is i have problems with my stomach thats why im in for pluging
     
  6. Mindless

    Mindless Gold Member

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    Thanks for putting me straight, and for the new information. Now that I think about it, I once tested the feel of rectal diazepam manufactured by Roche, rubbing a bit between thumb and forefinger.; it's oily just like propylene glycol. I found a couple of interesting articles:

    Polyethylene Glycol as a Solvent for Diazepam: Bioavailability and Clinical Effects after Intramuscular Administration, Comparison of Oral, Intramuscular and Rectal Administration, and Precipitation from Intravenous Solutions

    K. Korttila1,A. Sothman2,P. Andcrsson3
    Acta Pharmacologica et Toxicologica
    pages 104–117, July 1976. Volume 39, Issue 1.


    Article first published online: 13 MAR 2009
    DOI: 10.1111/j.1600-0773.1976.tb03161.x


    Abstract The bioavailability of diazepam (10 mg) was compared in a doubleblind cross–over manner in two studies on 15 healthy subjects. Serum diazepam levels were measured and the occurrence of pain at the injection site as well as fatigue was noted 20, 40, 60, 90 and 180 min. after the administration of 0.15 mg/kg of diazepam to seven subjects. Three intramuscular preparations were used: valium® (Roche), diapam® (Orion) and 301–K 2/74 (Orion). The last–mentioned preparation contained only half the propylene glycol contained in the other preparations, and polyethylene glycol (Macrogol) was the main solvent. The other eight subjects were similarly tested after the administration of diazepam orally, intramuscularly and rectally. In addition the precipitation of diazepam from intravenous solutions was investigated with diazepam in both solvents. Bioavailability and fatigue were similar after each treatment. 301–K 2/74 and its solvent placebo caused significantly less pain in the thigh than valium® or diapam®. The results suggest that an intramuscular injection of diazepam, deep into vastus lateralis muscle, and rectal and oral administration result in comparable bioavailability and clinical effects. A reduction in the amount of propylene glycol solvent used was associated with less pain at the injection site. When diapam® was injected into an infusion tube at a rate of 5 mg/min., the rate of infusion of 5 % glucose or 0.9 % saline had to be as fast as 20 ml/min. in order to prevent visible precipitation, whereas no precipitation was observed when 301–K 2/74 was injected at the 5 mg/min. rate into infusions moving at 5 ml/min. Further clinical studies with intramuscular and intravenous 301–K 2/74 are warranted.

    So propylene glycol and polyethylene glycol are both used as solvents in the preparation of diazepam solutions.

    I also came across this, from an article by Charles O'Sullivan and Simon Harvey:

    The use of rectal Diazepam for the treatment of prolonged convulsions in children

    Formulations
    Most studies have used injectable diazepam. The breaking of ampoules (10 mg/2 mL) and the use of needles by non-medical carers can be difficult and dangerous. If it is necessary to dilute diazepam, it is important to dilute it correctly as certain volumes of normal saline or dextrose can result in the precipitation of diazepam. Some institutions like the Royal Children's Hospital in Melbourne prepare 25 mL bottles of a rectal solution (1 mg/mL) using 50% propylene glycol in water. This is easy to use and does not expire for one year. Diazepam adsorbs to plastic and thus needs to be stored in glass. There are anecdotal reports of using diazepam oral mixture rectally, but its efficacy is not proven and thus cannot be recommended. Oil in water emulsions of injectable diazepam (e.g. Diazemuls) are slowly absorbed rectally and thus are inappropriate to use.

    The efficacy of rectal diazepam prepared from tablets is an unknown. It may be that there are ingredients that impede absorption, as in the case of diazemuls.

    I do have a two reservations about this preparation being done at home. I would recommend making only small or even single use batches of solution. When using any drug, it's important to be accurate about dosage.

    The solution should also be sterile, and it would be best to use diazepam tablets from a legitimate source. Some planning is needed to work out the best way of producing and storing a clean and safe solution for rectal use. If you plan to use glycols as a solvent, then they should be pharmacopoeia grade. Propylene Glycol can irritate mucosal membranes, use a small amount and dilute with sterile water.

    My last concern is that benzodiazepines are addictive, they interact with other medications and substances, and can have contra-indications. You would be prudent to discuss their use with your doctor.
     
    Last edited: Sep 26, 2011
  7. seroquel

    seroquel Newbie

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    should i first dissolve it in PG and then mix it with water or all at once?
    shit, i didnt know that it can hurt my mucosal membranes...hmm!?

    can i get PG at the drugstore? ...and what is that with the "pharmacopoeia grade" how can i spot if its the right PG

    sorry many many questions but its a bit difficult for me to translate all that stuff, im from germany, you know...

    thanks good night.

    seroquel added 38 Minutes and 26 Seconds later...

    but you agree that it is better to dissolve in PG for higher Bio Availability? instead of just mixing the pills with water...
     
    Last edited: Sep 26, 2011
  8. Mindless

    Mindless Gold Member

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    Propylene Glycol and Polyethylene Glycol are both used in e-juice for e-cigs, as a way of delivering nicotine in a vapour. I don't want to break any rules about sources discussion, you can probably work out the most useful search terms anyway.

    Pharmacopoeia grade products meet the standards used in the pharmaceutical industry. When you see the letters Ph.Eur. on the label of a medicine bottle, it means that the drug meets industry standards for the EU.

    You probably won't see that on the label for PG or PEG though, as it's not a medication itself. A good supplier will have a product specification sheet or certificate, and it will say Pharmacopoeia Grade on the product itself, and at least 99% of the contents will be PG. The label on my bottle of PG reads:

    PG/MPG
    Monopropylene Glycol
    1,2- PROPANEDIOL
    Pharmacopoeia Grade

    Diluting the PG before adding the diazepam would make it a less effective solvent. The idea is just to make it less irritating to the bowels.

    I don't really know how much PG to use. As little as possible, but sufficient to cover the powder. Crushing the pills exposes more of the surface area to the solvent. I also have no idea how long it would take for PG to absorb diazepam in tablet form, or even if diazepam tablets are miscible in PG.

    I have PG at home as I like to make my own e-juice, being a huge fan of vaping nicotine. It's also possible to prepare a vapable infusion of cannabis using PG.

    I just came across this:
    Solubility of Lamotrigine, Diazepam, Clonazepam, and Phenobarbital in Propylene Glycol + Water Mixtures at 298.15 K Ali Shayanfar, William E. Acree, Jr. and Abolghasem Jouyban.

    Biotechnology Research Center and Faculty of Pharmacy and Drug Applied Research Center, Tabriz University (Medical Sciences), Tabriz 51664, Iran, and Department of Chemistry, University of North Texas, Denton, Texas 76203-5070
    J. Chem. Eng. Data, 2009, 54 (3), pp 1153–1157

    DOI: 10.1021/je800931z

    Publication Date (Web): February 9, 2009

    Experimental solubilities of four antiepileptic drugs, that is, lamotrigine, diazepam, clonazepam, and phenobarbital in propylene glycol + water mixtures at 298.15 K were reported. The solubility of drugs was increased with the addition of propylene glycol, and the maximum values are observed in neat propylene glycol.

    So heating the PG to 25 degrees centigrade might help. My Uncle Baldylocks tells me that the the power adapter for his laptop provides a gentle heat source when preparing a cannabis infusion in PG.

    I can't find any references or citations regarding the effects on bioavailability of using PG to prepare a rectal diazepam solution. My impression is that it might improve bioavailability, as it at least seems to have been used effectively in a clinical setting.




     
    Last edited: Oct 21, 2011
  9. pecanpie

    pecanpie Newbie

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    I think you all are looking for this:


    Each mL of this sterile injection contains 5 mg diazepam compounded with 40% propylene glycol, 10% alcohol, 5% sodium benzoate and benzoic acid as buffers, and 1.5% benzyl alcohol as preservative.

    triple double u dot labeling dot pfizer dot com frontslash ShowLabeling dot aspx?id=4460

    pecanpie added 146 Minutes and 15 Seconds later...

    I'm too much of a noob to edit my post but those percentages are by weight and the remaining percentage is distilled water.
     
    Last edited: Jan 6, 2017