Development and testing of an improved parenteral formulation of phenytoin using 2-hydroxypropyl-β-cyclodextrin

J. Blanchard, S. O. Ugwu, R. Bhardwaj, R. T. Dorr

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The objective of this study was to increase the solubility of phenytoin by complexing it with varying concentrations of 2-hydroxypropyl-β- cyclodextrin (HPBCD) and create an entirely aqueous formulation with a pH significantly closer to physiologic pH (7.4). The phenytoin-HPBCD complexation was characterized using phase-solubility analysis at HPBCD concentrations ranging from 10 to 50% w/v over the pH range of 7.4-11.0. The two most promising formulations, i.e., a formulation consisting of 40% HPBCD at pH 10.4, and a second formulation consisting of 20% HPBCD at pH 11.0, were selected for further study. Both formulations were entirely aqueous and had a significantly decreased pH compared to the original commercial formulation (Parke-Davis, pH 12.0). These formulations also exhibited a significantly decreased tendency to precipitate in vitro. The tissue irritation potential of the 20% w/v HPBCD formulation at pH 11.0 was found to be reduced considerably compared to the commercial injection in a BALB/c mouse model.

Original languageEnglish (US)
Pages (from-to)333-338
Number of pages6
JournalPharmaceutical Development and Technology
Volume5
Issue number3
DOIs
StatePublished - Aug 15 2000

Keywords

  • 2-Hydroxypropyl-β-cyclodextrin
  • Complexation
  • In vitro precipitation
  • Phase solubility
  • Phenytoin
  • Skin toxicity

ASJC Scopus subject areas

  • Pharmaceutical Science

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