Abstract
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.
- Received September 11, 1986.
- Accepted February 18, 1987.
- Copyright © Parenteral Drug Association. All rights reserved.
PDA members receive access to all articles published in the current year and previous volume year. Institutional subscribers received access to all content. Log in below to receive access to this article if you are either of these.
If you are neither or you are a PDA member trying to access an article outside of your membership license, then you must purchase access to this article (below). If you do not have a username or password for JPST, you will be required to create an account prior to purchasing.
Full issue PDFs are for PDA members only.
Note to pda.org users
The PDA and PDA bookstore websites (www.pda.org and www.pda.org/bookstore) are separate websites from the PDA JPST website. When you first join PDA, your initial UserID and Password are sent to HighWirePress to create your PDA JPST account. Subsequent UserrID and Password changes required at the PDA websites will not pass on to PDA JPST and vice versa. If you forget your PDA JPST UserID and/or Password, you can request help to retrieve UserID and reset Password below.