Enteric-coated bacteriophage tablets for oral administration against gastrointestinal infections

Intestinal Pseudomonas aeruginosa is highly problematic in immunocompromised patients such as those in intensive care units in hospitals. Phage therapy is an attractive alternative or supplementary therapy to antibiotics as it not only kills multidrug-resistant bacteria, but also minimises the disruption of gut microflora. Solid oral dosage forms (i.e., tablets) have the potential to effectively deliver viable phages to the gastrointestinal tract, but formulation studies have been scarce. In this study, Pseudomonas-targeting phage PEV20 was used as a model to produce tablets suitable for oral delivery by utilising industry-scale tablet compression and tablet coating machines. Phage tablets were produced by (i) spray drying of phages, (ii) direct compression of the phage powders into tablets, and then (iii) tablet coating. The resulting phage tablets had negligible phage titre reduction throughout the process and passed the British Pharmacopeia tests, including friability, weight variation, disintegration and dissolution of the tablets as well as weight gain and disintegration (in 0.1 M HCl and pH 7.4 phosphate buffer) of coated tablets. The developed formulation method can be utilised to produce tablets containing other phages and phage cocktails that are effective against enteric bacterial infections.