caa a22 4500 477126138 CHVBK 20180405111650.0 cr unu---uuuuu 170330e19970901xx s 000 0 eng 10.1023/A:1012150722729 doi (NATIONALLICENCE)springer-10.1023/A:1012150722729 Effect of Ionic Strength on Solution Stability of PNU-67590A, A Micellar Prodrug of Methylprednisolone [Elektronische Daten] [Hirokazu Okamoto, Kiyoko Mori, Kumiko Ohtsuka, Hiroyuki Ohuchi, Hiroaki Ishii] Purpose. PNU-67590A is a water-soluble micellar prodrug of methyl-prednisolone (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°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. Plenum Publishing Corporation, 1997 stability nationallicence ionic strength nationallicence pH nationallicence critical micelle concentration nationallicence self-micellization nationallicence Okamoto Hirokazu Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut Mori Kiyoko Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut Ohtsuka Kumiko Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut Ohuchi Hiroyuki Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut Ishii Hiroaki Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1181-1185 0724-8741 14:9<1181 1997 14 11095 https://doi.org/10.1023/A:1012150722729 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012150722729 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Okamoto Hirokazu Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut NATIONALLICENCE 700 1- Mori Kiyoko Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut NATIONALLICENCE 700 1- Ohtsuka Kumiko Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut NATIONALLICENCE 700 1- Ohuchi Hiroyuki Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut NATIONALLICENCE 700 1- Ishii Hiroaki Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, 300-42, Ibaraki, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1181-1185 0724-8741 14:9<1181 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer