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

• Published in: European journal of pharmaceutics and biopharmaceutics 2005-10, Vol.61 (3), p.134-141
• Main Authors: Huyghebaert, Nathalie, Vermeire, An, Rottiers, Pieter, Remaut, Erik, Remon, Jean Paul
• Format: Article
• Language: English
• Subjects: Chemistry, Pharmaceutical; Drug Delivery Systems - methods; Drug Stability; Drug Storage; Eudragit; Ileum - metabolism; Interleukin-10 - administration & dosage; Interleukin-10 - biosynthesis; Inulin; Lactococcus lactis - genetics; Lactococcus lactis - physiology; Layering; Polymethacrylic Acids - administration & dosage; Recombinant Lactococcus lactis; Tablets, Enteric-Coated; Technology, Pharmaceutical; Viability
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2005.04.002

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 3 h 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 °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 °C), 80% of the initial L. lactis Thy12 remained viable in the Eudragit ® FS30D coated pellets.