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

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.

Measurement uncertainty of dissolution test of acetaminophen immediate release tablets using Monte Carlo simulations

“…Rotation speed was even more significant than time of dissolution. We believe this may be explained because acetaminophen is a high solubility drug (BCS Class I) (Kalantzi et al, 2006). Thus, the amount of acetaminophen dissolved in the range of time adopted in our study was close to the plateau level.…”

Enhancement of the Immediate Release of Paracetamol From Alginate Beads

“…one study found permeability to be 80% once absorbed. This enables it to fulfil the requirements of a biowaiver [13] so the dissolution profile can be used to evaluate the in-vitro drug release profile. Paracetamol has a bitter taste and this taste is difficult to be masked in the liquid formulations like syrup and suspension.…”

Stability Studies of a Mixture of Paracetamol and Ascorbic Acid, Prepared Extempore, at Elevated Temperature and Humidity Conditions

“…Paracetamol and ascorbic acid are commonly used organic ingredients of OTC medicinal products. Paracetamol is a widely used analgesic and antipyretic [7,8] while ascorbic acid, due to 2,3-endiol group in the molecule, may act both as an antioxidant or pro-oxidant, depending on the concentration [9]. As a result of ascorbic acid oxidation to dehydroascorbic acid one hydrogen atom is removed and an intermediate product is formed -the semi-hydroascorbic radical or two hydrogen atoms from the hydroxyl groups bonded to the 2nd and 3rd carbon atom [10].…”