Reformulation of a new vancomycin analog

an example of the importance of buffer species and strength.

Jennifer L H Johnson, Samuel H. Yalkowsky

Research output: Contribution to journalArticle

Abstract

The purpose of this research was to use our previously validated dynamic injection apparatus as a rapid method for screening pH-adjusted formulations of a new vancomycin analog, Van-An, for their potential to precipitate upon dilution. In 1 vial, Van-An was reconstituted according to the manufacturer's instructions. In a separate vial, the Van-An formulation's existing phosphate buffer species was supplemented with acetate buffer, which has a pKa in the desired range: between the pH values of the formulation (pH 3.9) and blood (pH 7.4). The formulations were injected using the dynamic injection apparatus into a flowing stream of isotonic Sorensen's phosphate buffer at rates of 0.25, 0.5, 1, and 2 mL/min. The peaks obtained with the spectrophotometer were reproducible for each injection rate/formulation combination. For the phosphate-buffered formulation, the least amount of precipitation was obtained at the 0.25 mL/min injection rate. Acetate buffer was able to substantially reduce such precipitation, even at the highest injection rate. The opacity peaks for the formulation with the acetate addition were significantly smaller (P < .05) than those obtained for the unaltered formulation at all 4 injection rates. The results suggest that acetate is a better buffer species than phosphate for the pH range defined. Furthermore, we present evidence to support a generally applicable approach to screening new formulations of drug products that may be clinically useful for reducing the incidence of phlebitis in humans.

Original languageEnglish (US)
JournalAAPS PharmSciTech
Volume7
Issue number1
StatePublished - 2006

Fingerprint

vancomycin
Vancomycin
Buffers
buffers
injection
Injections
Acetates
Phosphates
acetates
phosphates
drug formulations
screening
Phlebitis
Drug Compounding
blood pH
opacity
spectrophotometers
angle of incidence
rapid methods
Incidence

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

Cite this

Reformulation of a new vancomycin analog : an example of the importance of buffer species and strength. / Johnson, Jennifer L H; Yalkowsky, Samuel H.

In: AAPS PharmSciTech, Vol. 7, No. 1, 2006.

Research output: Contribution to journalArticle

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