Precipitation of pH solubilized phenytoin

Yosyong Surakitbanharn, Pahala Simamora, Gary H. Ward, Samuel H. Yalkowsky

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Precipitation of phenytoin often occurs as it is diluted by blood after intravenous injection. The presence and the amount of precipitate depend upon the initial pH and buffer capacity of the formulation vehicle. The prediction of phenytoin precipitation can be carried out in vitro using isotonic Sorensen's phosphate buffer (SPB) to simulate blood. An equation is developed to calculate the change in solubility resulting from the change in pH due to dilution. This equation is very difficult to solve analytically because it involves a high order polynomial. However, it can be solved numerically using a spreadsheet program. The relationship between pH or solubility and dilution can then be presented graphically. Therefore, the precipitation of any pH solubilized drug due to dilution under various conditions can be easily predicted. This is illustrated for several aqueous phenytoin solutions.

Original languageEnglish (US)
Pages (from-to)27-33
Number of pages7
JournalInternational Journal of Pharmaceutics
Issue number1
StatePublished - Aug 22 1994


  • Buffer
  • Formulation
  • Phenytoin
  • Precipitation
  • Solubility
  • pH equation

ASJC Scopus subject areas

  • Pharmaceutical Science


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