Afgiftemechanisme van tobramycine, Colistine en nystatine uit mondpasta voor selectieve decontaminatie van de mondholte

OBJECTIVE: To study the in vitro release of the compounds tobramycin sulphate (TS), Colistin sulphate (CS) and nystatin from the oral paste for selective oropharyngeal decontamination. DESIGN AND METHODS: The release of the active compounds was studied for 2 hours in a medium of phosphate buffer using various methods. Diffusion was studied with the paddle apparatus. Sedimentation was examined by spreading the paste on a filter paper and exposing this to the medium so that the particles could settle. The chewing motion was mimicked with a disintegration apparatus. Finally, the influence of 10, 20, 30 and 40% hydroxypropylmethylcellulose (HPMC) concentrations on drug release was studied. RESULTS: With the diffusion test the highest release was seen with TS (5.7%) and the lowest with nystatin (0.3%). With sedimentation the release of all three compounds was at least twice as high as with diffusion (TS: 14.0% vs 5.7%; CS: 6.3% vs 2.7%; nystatin: 0.9% vs 0.3%). Chewing motions influenced the release too (TS: 44.6%; CS: 16.4%; nystatin: 2.1%): the release was 2.5-3 times higher than with sedimentation. Increasing the HPMC concentration in the mouth paste improved the release of TS and CS, though it had little effect on nystatin (40% HPMC resulted in release of TS: 70.9%; CS: 37.5%; nystatin: 0.8%). CONCLUSION: Drug release from the mouth paste by diffusion is incomplete. Chewing motions and increasing HPMC concentrations (along with sedimentation) enhance the release of the active compounds. To improve release of TS and CS, more HPMC should be used in the formulation.