A 5% Glucose Infusion Fluid Provokes Significant Precipitation of Phenytoin Sodium Injection via Interruption of the Cosolvent Effect of Propylene Glycol.
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- Onuki Yoshinori
- Department of Pharmaceutics, Hoshi University
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- Ikegami-Kawai Mayumi
- Faculty of Pharmaceutical Sciences, Hoshi University
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- Ishitsuka Kazumi
- Department of Pharmaceutics, Hoshi University
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- Hayashi Yoshihiro
- Department of Pharmaceutics, Hoshi University
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- Takayama Kozo
- Department of Pharmaceutics, Hoshi University
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Abstract
The precipitation of phenytoin sodium injection provoked by mixing with infusion fluids renders its use in clinical practice difficult, as rapid intravenous (i.v.) push and i.v. infusion are supposed to be avoided. As some of its aspects remain unclear, this study tried to elucidate this precipitation mechanism. In particular, this study focused on the significant precipitation induced by glucose infusion fluid. The precipitation provoked by 5% glucose infusion fluid was obviously different from the precipitation that accompanied simple pH reduction, in terms of the growth mode and morphology of crystals. In addition, the effect of glucose was partially unrelated to pH reduction. NMR measurements including a two-dimensional nuclear Overhauser effect spectroscopy (2D-NOESY) spectrum indicated the specific interaction between glucose and propylene glycol, which is incorporated into phenytoin sodium injection as a solubilizing agent. These results led to the conclusion that this interaction was crucial for the precipitation of phenytoin, as it diminished the solubilizing effect of propylene glycol, resulting in the enhancement of the crystallization of phenytoin. The determination of phenytoin solubility in aqueous solutions at different pH values revealed that phenytoin incorporated in the admixture could be dissolved completely, as long as the injection was diluted with saline or water. These findings offer a profound insight into the formulation design of phenytoin sodium injection and its use in clinical practice.
Journal
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- Chemical and Pharmaceutical Bulletin
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Chemical and Pharmaceutical Bulletin 60 (1), 86-93, 2012
The Pharmaceutical Society of Japan
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Keywords
Details 詳細情報について
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- CRID
- 1390282679153820672
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- NII Article ID
- 130001852352
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- NII Book ID
- AA00602100
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- COI
- 1:STN:280:DC%2BC387isVClsA%3D%3D
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- ISSN
- 13475223
- 00092363
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- NDL BIB ID
- 024029762
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- PubMed
- 22223379
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed