Acid-base characteristics of bromophenol blue-citrate buffer systems in the amorphous state

Acid-base characteristics of bromophenol blue-citrate buffer systems in the amorphous state
December 2003
Jinjiang Li 1, Koustuv Chatterjee 2, Ales Medek 2, Evgenyi Shalaev 2, George Zografi 1 *
1School of Pharmacy, University of Wisconsin-Madison, Wisconsin 53705
2Groton Laboratories, Pfizer, Inc., Groton, Connecticut 06340
Journal of Pharmaceutical Sciences, Volume 93, Issue 3 , Pages 697 - 712
You can view the abstract online. A subscription is required to view the full text or it can be purchased online.
Abstract
In this study, we have examined the acid-base characteristics of various citrate buffer systems alone and in the presence of the pH indicator dye, bromophenol blue, in aqueous solution, and after lyophilization to produce amorphous material. Fourier transform Raman and solid-state nuclear magnetic resonance spectroscopy have been used to monitor the ratio of ionized to un-ionized citric acid under various conditions, as a function of initial pH in the range of 2.65-4.28. Ultraviolet-visible spectrophotometry was used to probe the extent of proton transfer of bromophenol blue in the citrate buffer systems in solution and the amorphous state. Spectroscopic studies indicated greater ionization of citric acid and bromophenol blue in solution and the solid state with increasing initial solution pH, as expected. Fourier transform Raman measurements indicated the same ratio of ionized to un-ionized citrate species in solution, frozen solution, and the amorphous state. It is shown that the ratio of species at any particular initial pH is primarily determined by the amount of sodium ion present so as to maintain electroneutrality and not necessarily to the fact that pH and pKa remain unchanged during freezing and freeze drying. Indeed, for bromophenol blue, the relative ultraviolet-visible intensities for ionized and un-ionized species in the amorphous sample were different from those in solution indicating that the extent of protonation of bromophenol blue was significantly lower in the solid samples. It is concluded that under certain conditions there can be significant differences in the apparent hydrogen activity of molecules in amorphous systems. ? 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:697-712, 2004
Keywords
amorphous ? solid-state ? acid-base equilibria ? pH ? lyophilization ? glass transition ? Raman spectroscopy ? NMR