Effect of spatial distribution of contaminant microorganisms within tablet formulations on subsequent inactivation through compaction
Plumpton, E.J.; Gilbert, P.; Fell, J.T.
International Journal of Pharmaceutics (Kidlington) 30(2-3): 237-240
A wet granulation process, employing an aqueous suspension of Bacillus megaterium spores as binder, was used to prepare contaminated granules of three direct compression vehicles, Emdex, lactose and potassium chloride. Granules were also prepared with sterile water as binder and directly contaminated by dry mixing with B. megaterium spores, as were the original direct compression vehicles. Particle size distributions for the granules and the direct compression vehicles were similar. Survival of B. megaterium was assessed, following compaction (500 mg) at various pressures (0-271 MN .cntdot. m-2) using a 1 cm flat-faced punch and a 10 ton hydraulic press. In all cases the degree of killing was directly proportionate to the compaction pressure. For those materials compacting by fracture, lactose and Emdex, then the degree of killing was directly proportionate to the compaction pressure. For those materials compacting by fracture, lactose and Emdex, then the degree of killing was similar for the dry contaminated direct compression vehicle and those granules prepared with contaminated binding fluid, but significantly greater in the dry contaminated granules and greater overall for lactose rather than Emdex. For potassium chloride, a material which plastically deforms, then the degree of killing was significantly enhanced by incorporation of the contaminant into the binding fluid.