I am trying to dissolve API of Acetaminophen in Saline/Water to induced Hepatotoxicity in Mice/Rats. But it not dissolved. PCM is soluble in Ethanol and DMSO. May I use Ethanol/DMSO to dissolve the PCM? I have gone through the number of Research paper, but did not found the clear answer.
Are you trying to dissolve the over-the-counter available Tylenol tablet or is the paracetamol purchased from some place like Sigma? Often the pills and tablets we get from the pharmacy will not be fully soluble in water because of the binding agents that keep the tablet together.
So I would definitely suggest purchasing the active compound (acetaminophen/paracetamol) from Sigma. For IP injections, first dissolve in DMSO and then, dilute to your desired dosage (while also making sure that the final concentration of DMSO is
You can use the DMSO as solubilizing agent, but DMSO in Cell line studies has reported some toxicity. I don't have much idea about in mice/rat hepatotoxicity.
U should try to dissolve in water, heat for some time use magnetic stirrer
You should dissolve it in water but it probably wont be clear solution due to other ingredients in capsule/tablet that you are using. Thus fine suspension of that should be good for oral application.
if it is not soluble in water try to dissolve it in corn oil or groundnut oil, still if you won't find solution then try to suspend the API in 0.1 to 0.5 % carboxy methyl cellulose solution and induce hepatotoxicity in rats/mice.
Rats are not a good model for asessing acetaminophen toxicity :
"rats are resistant to APAP toxicity. As a result, mice are the preferred species for mechanistic studies. Furthermore, recent work has shown that the mechanisms of APAP toxicity in humans are similar to mice. Nevertheless, some investigators still use rats. New mechanistic information from the last forty years invites a reevaluation of the differences between these species" "we found that rats were highly resistant to APAP toxicity. Although overall APAP metabolism was similar in both species, mitochondrial protein adducts were significantly lower in rats. Accordingly, rats also had less oxidative stress. Finally, while mice showed extensive activation and mitochondrial translocation of JNK, this could not be detected in rat livers. These data support the hypothesis that mitochondrial dysfunction is critical for the development of necrosis after APAP treatment. Because mitochondrial damage also occurs in humans, rats are not a clinically relevant species for studies of APAP hepatotoxicity."
Toxicol Appl Pharmacol. 2012 Nov 1;264(3):387-94.
Are you trying to dissolve the over-the-counter available Tylenol tablet or is the paracetamol purchased from some place like Sigma? Often the pills and tablets we get from the pharmacy will not be fully soluble in water because of the binding agents that keep the tablet together.
So I would definitely suggest purchasing the active compound (acetaminophen/paracetamol) from Sigma. For IP injections, first dissolve in DMSO and then, dilute to your desired dosage (while also making sure that the final concentration of DMSO is
You can make paracetamol suspension and administer by oral route. Use 0.5% Sod CMC as suspending agent, even you can use 2.5% gum acacia.
You can try with a drug delivery system (for in vivo experiment): in this way you can target your device drug-conjugated directly at liver. For in vitro experiments you can try with some biocompatible co-solvent as SDS.
As your rout of choice is oral route youcan give suspention of your drug.
Here you are inducing hepatotoxicity then you choose pure drug only,,,,,not tab or other preperations
Try to prepare paracetamol suspention by using suspending agents like tween 80.
Excipients like propylene glycol, tween 80 and others might interfere with the function of hepatic enzymes and transport proteins thus altering paracetamol toxicity!
http://pubs.acs.org/doi/abs/10.1021/mp3001815
How much paracetamol do you have to dissolve? Did you consider adjustment of pH to improve aquous solubility?
A commercial version of an IV human formulation named OFIRMEV is available in the US. I suppose it could be used orally if desired. This would avoid the need to dissolve it yourself.
http://www.ofirmev.com/safety.aspx?gclid=CLzV18zUwsACFcRcMgodd00Alw
why not try 2 % gum acacia, it is not toxic and can be taken by humans
Try to use 0.5% CMC, we have obtained good results. Do not forget to use a control group with vehicle alone.
You can use any suspending agent like gum acacia,sodium CMC,tween,peg and keep a vehicle control gropup
1. dissolve in a mixture of propylene glycol and ethanol
2. use nanotechnology technique to get it dissolve in water
Dear Ashu,
thanks for this question. I was looking for that too. Did you succeed using any of this methods? This dose (500mg/b.w. )is a nice to induce liver toxicity?
Regards
Ashu,
You can make suspention of paracetamol in water using tween 80 as suspending agent and soothing also this was followed for every drug which can administered p.o.
Just weigh ur paracetamol and put in mortar and add 1-2 drops of tween and triturate it then add water to makeup.............
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology