Effect of ionic strength on solution stability of PNU-67590A, a micellar prodrug of methylprednisolone

• Published in: Pharmaceutical research Vol. 14; no. 9; pp. 1181 - 1185
• Main Authors: OKAMOTO, H, MORI, K, OHTSUKA, K, OHUCHI, H, ISHII, H
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.09.1997; Springer Nature B.V
• Subjects: Biological and medical sciences; Drug Stability; General pharmacology; Immunomodulators; Ions; Medical sciences; Methylprednisolone - analogs & derivatives; Methylprednisolone - chemistry; Methylprednisolone - metabolism; Methylprednisolone - pharmacology; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Prodrugs - chemistry; Antineoplastic agent; Corticosteroid; Stability; Antiinflammatory agent; Micelle; Prodrug; Metabolism; Physical properties; Hydrolysis; Acyl group; Ionic strength; Adrenal hormone; Immunosuppressive agent; Prednisolone
• ISSN: 0724-8741; 1573-904X
• 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.