Effect of Ionic Strength on Solution Stability of PNU-67590A,A Micellar Prodrug of Methylprednisolone |
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Authors: | Okamoto Hirokazu Mori Kiyoko Ohtsuka Kumiko Ohuchi Hiroyuki Ishii Hiroaki |
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Institution: | (1) Pharmacia & Upjohn, Tsukuba Research Laboratories, 23 Wadai, Tsukuba, Ibaraki, 300-42, Japan |
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Abstract: | 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. |
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Keywords: | stability ionic strength pH critical micelle concentration self-micellization |
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