Salivary nystatin concentrations after administration of an osmotic controlled release tablet and a pastille.

Abstract

Mucosal oral therapeutic system (MOTS) is a controlled-release osmotic system for oral cavity therapy. MOTS (nystatin) is designed to deliver approximately 200,000 units of nystatin over several hours. A crossover study was conducted in five healthy volunteers to evaluate the amount of nystatin released (based on residual drug content) when the system is held in the mouth for 30 min, 1 h, and 2 h, and to compare these concentrations with those achieved with a Mycostatin (nystatin) pastille. An average of 37% of the nystatin content was released intra-orally from MOTS during 2 h in the mouth, which was very similar to the percentage delivered in vitro. Mean salivary drug concentrations were as follows: 279 micrograms.ml-1 at 30 min; 654 micrograms.ml-1 after 1 h; and 532 micrograms.ml-1 at 2 h. These concentrations consistently exceeded those produced by the pastille at the same time points. Fifteen minutes after placement of the pastille in the mouth (i.e., immediately after its dissolution) mean nystatin concentrations reached 746 micrograms.ml-1 but fell rapidly to 13.2 micrograms.ml-1 at 30 min, 7.2 micrograms.ml-1 at 1 h, and 5.6 micrograms.ml-1 at 2 h. The study demonstrates that MOTS maintains high salivary nystatin concentrations throughout a 2 h dosing interval.