From the pharmaceutical to the clinical: the case for effervescent paracetamol in pain management. A narrative review

Curr Med Res Opin. 2021 Jun;37(6):1039-1048. doi: 10.1080/03007995.2021.1902297. Epub 2021 Apr 5.


Objective: Paracetamol has an established place in the management of mild-to-moderate pain, but has certain limitations, including varying bioavailability, and potential hepatotoxicity if taken in overdose. Effervescent formulations may help to overcome these limitations.

Methods: Pubmed searches, with no limits on date or language, were conducted in February 2020. Further references were identified from the reference lists of retrieved articles, and from the authors' knowledge of the field.

Results: Effervescent formulations contain an organic acid (usually citric acid) and carbonate or bicarbonate salts (usually sodium bicarbonate). Upon contact with water, these react to form carbon dioxide, which facilitates the disintegration of the tablet and dissolution of the active drug. Moreover, sodium bicarbonate dose-dependently increases gastric emptying, which together with rapid dissolution facilitates drug absorption. In pharmacokinetic studies, effervescent formulations result in faster absorption of paracetamol than conventional oral formulations, and this translates into a faster onset of analgesia in clinical trials. Effervescent paracetamol has a favorable safety profile, with good tolerability. Importantly, the sodium content of some preparations does not appear to increase cardiovascular risk under real world conditions. Effervescent formulations may also offer advantages in terms of ease of administration and palatability.

Conclusions: Effervescent formulations of paracetamol result in faster drug absorption, and hence more rapid analgesia, than oral tablets, and offer a favorable tolerability and safety profile. The use of such formulations may therefore help to promote appropriate use of paracetamol.

Keywords: Drug formulation; efficacy; paracetamol; pharmacokinetics; safety.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetaminophen*
  • Biological Availability
  • Cross-Over Studies
  • Humans
  • Pain Management*
  • Tablets


  • Tablets
  • Acetaminophen