Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol)

J Pharm Sci. 2006 Jan;95(1):4-14. doi: 10.1002/jps.20477.

Abstract

Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of absorption. However, some studies show differences in rate of absorption between brands and formulations. In particular, sodium bicarbonate, present in some drug products, was reported to give an increase in the rate of absorption, probably caused by an effect on gastric emptying. In view of Marketing Authorizations (MAs) given in a number of countries to acetaminophen drug products with rapid onset of action, it is concluded that differences in rate of absorption were considered therapeutically not relevant by the Health Authorities. Moreover, in view of its therapeutic use, its wide therapeutic index and its uncomplicated pharmacokinetic properties, in vitro dissolution data collected according to the relevant Guidances can be safely used for declaring bioequivalence (BE) of two acetaminophen formulations. Therefore, accepting a biowaiver for immediate release (IR) acetaminophen solid oral drug products is considered scientifically justified, if the test product contains only those excipients reported in this paper in their usual amounts and the test product is rapidly dissolving, as well as the test product fulfils the criterion of similarity of dissolution profiles to the reference product.

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / chemistry
  • Acetaminophen / pharmacokinetics*
  • Administration, Oral
  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / chemistry
  • Analgesics, Non-Narcotic / pharmacokinetics*
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Dosage Forms
  • Excipients
  • Solubility
  • Therapeutic Equivalency

Substances

  • Analgesics, Non-Narcotic
  • Dosage Forms
  • Excipients
  • Acetaminophen