Toxicological assessment of Anionic Methacrylate Copolymer: I. Characterization, bioavailability and genotoxicity

Regul Toxicol Pharmacol. 2016 Dec:82:39-47. doi: 10.1016/j.yrtph.2016.11.009. Epub 2016 Nov 4.

Abstract

Anionic Methacrylate Copolymer (AMC) is a fully polymerized copolymer used in the pharmaceutical industry as an enteric/delayed-release coating to permit the pH-dependent release of active ingredients in the gastrointestinal tract from oral dosage forms. This function is of potential use for food supplements. Oral administration of radiolabeled copolymer to rats resulted in the detection of chemically unchanged copolymer in the feces, with negligible absorption (<0.1%). AMC is therefore determined not to be bioavailable. Within a genotoxicity test battery AMC did not show any evidence of genotoxicity in bacteria and mammalian cells. Furthermore, no genotoxic effects occurred in vivo within a micronucleus test. There would therefore appear to be no safety concerns under intended conditions of oral use for the discussed toxicological endpoints.

Keywords: Ames test; Anionic Methacrylate Copolymer; Chromosome aberration test; Coating agent; EUDRAGIT(®) FS; EUDRAGUARD(®); Food additive; Genotoxicity; Micronucleus assay; Mouse lymphoma assay.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Excipients / administration & dosage
  • Excipients / chemistry
  • Excipients / pharmacokinetics
  • Excipients / toxicity*
  • Feces / chemistry
  • Female
  • Gastrointestinal Absorption
  • Male
  • Methacrylates / administration & dosage
  • Methacrylates / chemistry
  • Methacrylates / pharmacokinetics
  • Methacrylates / toxicity*
  • Mice
  • Micronuclei, Chromosome-Defective / chemically induced
  • Micronucleus Tests
  • Mutagenesis
  • Polymethacrylic Acids / administration & dosage
  • Polymethacrylic Acids / chemistry
  • Polymethacrylic Acids / pharmacokinetics
  • Polymethacrylic Acids / toxicity*
  • Rats, Sprague-Dawley
  • Risk Assessment
  • Toxicokinetics

Substances

  • Excipients
  • Methacrylates
  • Polymethacrylic Acids
  • methylmethacrylate-methacrylic acid copolymer