RT Journal Article
SR Electronic
T1 The Effects of Cosolvents on the Action of Pharmaceutical Buffers
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 45
OP 49
VO 41
IS 2
A1 Rubino, Joseph T.
YR 1987
UL http://journal.pda.org/content/41/2/45.abstract
AB The pKa values of a number of pharmaceutical conjugate buffer acids were determined in several cosolvent-water mixtures. The pKa values were observed to differ by as much as 2pH units from the aqueous pKa values. Increases in the pKa values of acidic buffer species were observed in all cases except boric acid in polyol-water mixtures. This was presumed to be due to a well-known complexation interaction between glycols and borate. Decreases in pKa were observed for the amine buffers except glutamic acid where the charges on the protonated and unprotonated species are different from other amines. A weak interaction between THAM and glycerol was evident from an unexpected increase in pKa with cosolvent concentrations. Unexpectedly high pKa changes in dimethylsulfoxide-water mixtures for some of the solutes demonstrate the importance of nonelectrostatic solvent effects on the changes in pKa values in semiaqueous solvent systems. These data can be used to determine the pH range over which various buffers will be effective in different cosolvent-water mixtures. In addition, the simultaneous effects of dilution on the pHp of a poorly soluble drug and pH of formulations containing cosolvent-buffer mixtures is considered. It is shown that a consideration of these effects can be used to develop parenteral dosage forms which will have improved physical stability when diluted during injection or upon mixing with infusion solutions.