Development of an enteric-coated, layered multi-particulate formulation for ileal delivery of viable recombinant Lactococcus lactis

Eur J Pharm Biopharm. 2005 Oct;61(3):134-41. doi: 10.1016/j.ejpb.2005.04.002. Epub 2005 Jun 20.

Abstract

Layering of recombinant hIL-10 producing Lactococcus lactis (L. lactis Thy12) on inert carriers is a promising technique for the preparation of a multi-particulate formulation of viable, hIL-10 producing L. lactis. To improve viability after layering and storage, L. lactis Thy12 was layered in different matrices (10% skim milk and/or 2.5, 5, 10% inulin). After layering, the highest viability was obtained in the 10% skim milk supplemented with 5% inulin matrix (8.7%). However, upon storage, 10% skim milk alone yielded the highest viability. Thereby, layered L. lactis Thy12 showed superior long term stability in comparison with freeze-dried L. lactis Thy12. The layering process was performed during 3h without encountering technical problems, with good layer consistence and constant viability. Enteric properties were obtained with a 30% Eudragit L30D-55 or 15% Eudragit FS30D coating and maintained during an initial six months storage period (-20 degrees C/20% RH). After in vitro simulation of the gastric stage, only 5% of the bacteria remained viable in Eudragit L30D-55 coated pellets, contrary to 85% in Eudragit FS30D coated pellets, indicating its superior protective capacity against gastric fluid. After eight months storage (-20 degrees C), 80% of the initial L. lactis Thy12 remained viable in the Eudragit FS30D coated pellets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry, Pharmaceutical
  • Drug Delivery Systems / methods*
  • Drug Stability
  • Drug Storage
  • Ileum / metabolism*
  • Interleukin-10 / administration & dosage*
  • Interleukin-10 / biosynthesis
  • Lactococcus lactis / genetics*
  • Lactococcus lactis / physiology
  • Polymethacrylic Acids / administration & dosage
  • Tablets, Enteric-Coated
  • Technology, Pharmaceutical

Substances

  • Polymethacrylic Acids
  • Tablets, Enteric-Coated
  • Interleukin-10
  • methylmethacrylate-methacrylic acid copolymer