PURPOSE: PNU-67590A is a water-soluble micellar prodrug of methylprednisolone (MP). The major products of degradation of PNU-67590A are MP by hydrolysis and methylprednisolone 17-suleptanate (17-E) by 21-->17 acyl migration. The effect of ionic strength on micelle formation and stability of PNU-67590A in aqueous solution was examined. METHODS: PNU-67590A solutions at pH 2 and 8 and ionic strength of 0.05, 0.1, 0.2, and 0.4 M were maintained at 25 degrees C in the dark to measure MP and 17-E levels over time. RESULTS: The rate of degradation of micellar PNU-67590A at pH 8 was less than that of monomeric PNU-67590A, and vice versa at pH 2. Increase in ionic strength decreased both the critical micelle concentration of PNU-67590A and the degradation of micelle PNU-67590A at both pHs, resulting in improved overall stability of PNU-67590A. CONCLUSIONS: Formulation of PNU-67590A in a concentrated solution with high ionic strength will maximize stability and shelf-life.
PURPOSE: PNU-67590A is a water-soluble micellar prodrug of methylprednisolone (MP). The major products of degradation of PNU-67590A are MP by hydrolysis and methylprednisolone 17-suleptanate (17-E) by 21-->17 acyl migration. The effect of ionic strength on micelle formation and stability of PNU-67590A in aqueous solution was examined. METHODS: PNU-67590A solutions at pH 2 and 8 and ionic strength of 0.05, 0.1, 0.2, and 0.4 M were maintained at 25 degrees C in the dark to measure MP and 17-E levels over time. RESULTS: The rate of degradation of micellar PNU-67590A at pH 8 was less than that of monomeric PNU-67590A, and vice versa at pH 2. Increase in ionic strength decreased both the critical micelle concentration of PNU-67590A and the degradation of micelle PNU-67590A at both pHs, resulting in improved overall stability of PNU-67590A. CONCLUSIONS: Formulation of PNU-67590A in a concentrated solution with high ionic strength will maximize stability and shelf-life.