Kouimtzi, Maria; (2000) Survival of bacteria in pellets, tablets and capsules. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The survival of probiotic and model organisms in pellets, tablets and capsules was investigated in an attempt to formulate stable solid oral dosage forms, containing probiotic bacteria. Two new incorporation methods were investigated; direct incorporation of bacterial suspensions into pellet formulations and the freeze drying of mixtures of bacterial suspensions with tableting excipients. The mixing of freeze dried bacteria with tableting excipients was also investigated. Gram-negative aerobic {Escherichia coli), Gram-positive aerobic (Staphylococcus saprophyticus and Bacillus subtilis) and Gram-positive anaerobic (Bifidobacterium longum and Lactobacillus acidophilus) vegetative bacteria, together with spores of Bacillus subtilis, were introduced separately into a formulation, which was extruded, spheronised and dried to produce pellets. Spores survived all stages of the process. Survival levels of the Gram-positive organisms after extrusion, spheronisation and drying were significantly higher than the Gram-negative E. coli. The effects of extrusion speed, extrusion die length to radius ratio, and extrusion pressure on the viability of the more sensitive E. coli were investigated. The level of killing was not affected by extrusion speed or die length to radius ratio. However, survival was inversely proportional to extrusion pressure over the range 1-8000 kPa. A range of compaction forces was employed to investigate the susceptibility of L acidophilus, incorporated into a lactose and a microcrystalline formulation mix, to the forces produced by tableting. Samples from both mixtures were compressed at pressure ranging from 1-300 MPa. A strong negative correlation between bacterial survival and compaction pressure was observed, suggesting that survival decreased with increase in tablet compaction pressure. Mechanical strength and friability tests showed that all tablets produced were of acceptable strength. Results show that L. acidophilus can be successfully inoculated into a tablet formulation providing the compaction pressure is monitored carefully. Stability testing of the L. acidophilus formulations showed that freeze dried L. acidophilus does not remain viable after eight and nine days in the mixtures with microcrystalline cellulose and lactose respectively. Capsule filling with the L. acidophilus/lactose mixture was proved to be the most successful approach, since the lethal effects of drying and pressure were kept to a minimum. Furthermore, these capsules were successfully coated at room temperature with an ethylcellulose/amylose colon-specific coat, without loss of bacteria viability. Five percent coat thickness was shown to withstand simulated gastric and intestinal conditions, whilst remaining susceptible to degradation in the colon by bacterial enzymes.

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