Optimisation of an enteric coated, layered multi-particulate formulation for ileal delivery of viable recombinant...

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.