Effect of ionic strength on solution stability of PNU-67590A, a micellar prodrug of methylprednisolone.
OBJECTIVE
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.
Okamoto
H
H
Pharmacia & Upjohn, Tsukuba Research Laboratories, Ibaraki, Japan. hirokazu.okamoto@am.pnu.com
Mori
K
K
Ohtsuka
K
K
Ohuchi
H
H
Ishii
H
H
D004355:Drug Stability; D007477:Ions; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry*
D007477:Ions; D011355:Prodrugs; C052305:methylprednisolone suleptanate; D008775:Methylprednisolone