pH in a viscous formulation

[mtnshawn]

Colleagues-
Our formulary matrix consists of approxinmately 15% polymer, 8% API, 2% EtOH, 0.2% preservative and EDTA.

Obviously this solution is not a true aqueous solution, so pH measurement is a little dicey. We do generate reproducible results, but their accuracy is a concern.

Is there a good titremetric or conductance procedure out there for determining pH in complex matrices?

Maybe a more relevant question would be: What is the most accurate technique for determining pH in non-aqueous solutions?

Tnx in advance for thoughts/input.

Shawn

[Bill Tindall]

First, let me say that there is nothing wrong, imprecise or inaccurate about measureing pH in your solution, and the measurement will be "blessed" by the internationally recognized definitions of pH, NIST for example, providing you document your calibration procedure. Calibration in water will be suitable for this task. The presence of the polymer may require that you use a "leaky" junction. I would suggest a sleeve type junction for these measurements.

That said, why are you making this measurement? Whether pH is the best way to meet your need as well as how the pH measurement is to be interpreted will depend on your answer to the "why" question. What is API? I presume the polymer is water soluble. Is it charged?

You can not determine pH from a titration of this solution, but titration would be the most precise way to determine total acidity or bascity.

[mtnshawn]

Bill-
Thanks for the response. Some time ago, I remember you providing great detail on the process of pH determination, measurement and the various pitfalls associated with the measurement.

The formulation is a "mouth wash" for radiotherapy patients. The lesions in their mouth are quite sensitive to acidic conditions, so we have a pH spec of 6.0 to 6.5.

Polymer is not charged, but we do see some drift in pH from completion of batch to t=0 (batch is bottled and submitted for full release testing).

Silly question, but can you tell me what the difference b/t pH and total acidity is? It may be that instead of evaluating pH, we should really be evaluating total acidity which may give us a more accurate result and be a better measurment for the intended purpose.
s

[Bill Tindall]

As I understand it......
It is known that if the pH is between xxx and yyy that the stuff meets fitness for use. So the problem is to ensure by testing pH that batches will be between xxx and yyy.

Facts: You didn't tell me what the polymer was but I will assume its ionic and water soluble. As such it will result in a significant juction potential. But, this is not a problem so long as the composition of the stuff does not greatly change among measurements (which means this unknown junction potential will not change among measurements) . The electode should perform without problem.

Recommendations ...Calibrate electrode in water with buffers that bracket the control pH range. Alternatively if the control range is small I would calibrate with one standard in the target range (I think this will be more precise). If you get drifty readings its probably the junction potential going for a stroll. A leaky junction should help so use a reference with a sleeve junction. Comparative measurements among solutions of similar composition can then be reliably performed. I suspect mouth sensitivity is more a function of pH than total acidity, so you probably need to measure pH.

Limitations.. for assorted reasons you can not equate the pH reading you obtain to -log (hydrogen ion activity) but this in not a problem becasue you aren't dong equilibria calculations in this solution, just ensuring it meets a target.

Total acidity and pH. The pH of an acetate buffer made from 0.05 M sodium acetate and 0.05 M acetic acid is about 4.7, If you titrate this solution you will find it contains 0.05 equivalents of acid per liter (total acidity is 0.05 equivalents/ liter)

Hope this helps...................

[mtnshawn]

Bill-
thanks a lot. Great comments, good advice.

shawn

[HW Mueller]

In physical organic chemistry we used to distinguish between general acid catalysis (due to H+) and specific acid catalysis (the acid present, like HOAC). I wonder whether anybody has looked at exactly what causes the mentioned sensitivity, I only know that the fungal, etc., infections in these patients are horrendous.