Okamoto H, Mori K, Ohtsuka K, Ohuchi H, Ishii H
Pharmacia & Upjohn, Tsukuba Research Laboratories, Ibaraki, Japan.
Pharm Res. 1997 Sep;14(9):1181-5. doi: 10.1023/a:1012150722729.
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.
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.
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.
Formulation of PNU-67590A in a concentrated solution with high ionic strength will maximize stability and shelf-life.
PNU - 67590A是甲基泼尼松龙（MP）的水溶性胶束前药。PNU - 67590A降解的主要产物是通过水解产生的MP以及通过21→17酰基迁移产生的17 - 硫辛酸甲酯泼尼松龙（17 - E）。研究了离子强度对PNU - 67590A在水溶液中胶束形成和稳定性的影响。
将pH值为2和8、离子强度分别为0.05、0.1、0.2和0.4 M的PNU - 67590A溶液在25℃黑暗条件下保存，以测定不同时间的MP和17 - E水平。
在pH 8时，胶束型PNU - 67590A的降解速率低于单体型PNU - 67590A，而在pH 2时情况相反。离子强度的增加降低了PNU - 67590A的临界胶束浓度以及在两种pH值下胶束型PNU - 67590A的降解，从而提高了PNU - 67590A的整体稳定性。
将PNU - 67590A配制成高离子强度的浓缩溶液可使稳定性和保质期最大化。
