title: Optimisation of an enteric coated, layered multi-particulate formulation for ileal delivery of viable recombinant Lactococcus lactis.
abstract: Layering of pellets with recombinant Lactococcus lactis Thy 12 was optimised for the production of a dosage form with a high load of viable recombinant L. lactis. Shear stress induced during the atomisation and the type of carrier used for the layering process did not influence the viability. A 5% lactose matrix resulted in the highest viability of L. lactis (8.9+/-1.7%) which could be maintained for at least 12 months at -20 degrees C. A higher bacterial cell load on the pellets was obtained using a longer process time, but the addition of 10% skim milk was essential to maintain the stabilising capacity of the matrix. Increasing the load of viable L. lactis was also possible using a higher bacterial cell concentration of the layering suspension and increasing the amount of stabilising matrix to 10% lactose/20% skim milk, yielding a formulation with 1.7 x 10(9)cfu/100 mg pellets. To protect the bacteria during gastric passage and to obtain ileum targeting, the formulation was enteric coated with 5% Eudragit FS30D, but after coating and gastric residence for 2 h HCl about 1% of the bacteria remained viable. Application of a subcoating, previous to enteric coating, did not result in a higher viability.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Poelvoorde
authors.forename: Nathalie
authors.initials: N
authors.lastname: Huyghebaert
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Remon
mesh_terms: D000818:Animals; D002482:Cellulose; D002626:Chemistry, Pharmaceutical; D003424:Crohn Disease / Q000628:therapy; D003470:Culture Media; D016503:Drug Delivery Systems; D005079:Excipients; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D013294:Lactococcus lactis / Q000737:chemistry*; D008892:Milk / Q000737:chemistry; D011109:Polymethacrylic Acids; D011142:Polyvinyl Alcohol / Q000737:chemistry; D013213:Starch; D013608:Tablets, Enteric-Coated; D013936:Thymidine / Q000008:administration & dosage
chemical_list: D003470:Culture Media; D005079:Excipients; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; D016753:Interleukin-10; C038300:methylmethacrylate-methacrylic acid copolymer; D011142:Polyvinyl Alcohol; D002482:Cellulose; D013213:Starch; C109691:microcrystalline cellulose; D013936:Thymidine