title: Development of an enteric-coated, layered multi-particulate formulation for ileal delivery of viable recombinant Lactococcus lactis.
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.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Huyghebaert
authors.forename: An
authors.initials: A
authors.lastname: Vermeire
authors.forename: Pieter
authors.initials: P
authors.lastname: Rottiers
authors.forename: Erik
authors.initials: E
authors.lastname: Remaut
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
mesh_terms: D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage; D007082:Ileum / Q000378:metabolism*; D016753:Interleukin-10 / Q000008:administration & dosage* / Q000096:biosynthesis; D013294:Lactococcus lactis / Q000235:genetics* / Q000502:physiology; D011109:Polymethacrylic Acids / Q000008:administration & dosage; D013608:Tablets, Enteric-Coated; D013678:Technology, Pharmaceutical
chemical_list: D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; D016753:Interleukin-10; C038300:methylmethacrylate-methacrylic acid copolymer