Chromatography Forum

Hello,

I have a method for more or less soft pharmaceutical tablets, which are dissolved in the following mixture:

- dissolve 2 g sodium octanesulfonate in 300 mL water
- adjust the pH with acetic acid to 3.5
- mix with 700 mL methanol

I checked the "pH" of the final mixture: 4.7

I have also a much harder tablet with the same analyte. In the mentioned mixture, the tablet disintegrates after 120 minutes ultrasonication. This is due to the high percentage of organic. Thus, I would try to go down with the percentage to 20%.

Thus, I have to dissolve 2 g sodium octanesulfonate in 800 mL of water. And now? What would you dou?

- adjust the pH with acetic acid to 3.5 and mix with 200 mL methanol?
- add 200 mL methanol and adjust the "pH" of the mixture with acetic acid to 4.7?
- perform any special pH calculations and adjust according to the result?

Thank you very much for your help.

Florian

Hello

If your pH meter is calibrated with buffers prepared in water you should adjust pH for buffer and then mix it with organic solvent. If you measure pH after you mix buffer with organic solvent the measured pH is not real pH value (however sometimes it could be close) because calibration buffers are prepared in water).

Regards

Tomasz Kubowicz

If the methanol is slowing the disintegration of the tablet, but is needed due to the solubility of the API, then why not add the methanol subsequently?

The process might look like this:

1. Add 1 tablet in X mL buffer
2. Sonicate until the tablet is completely disintegrated
3. Add X mL methanol and shake vigorously
4. Fill up to volume with a premixed methanol/buffer solvent, or mobile phase or whatever relevant.

Best Regards

Dear both,

thanks a lot for your replies.

Danko: I do not like these subsequent water / organic additions due to the effects of volume contraction and temperature rising. My preferred operation is to mix aqueous part and organic part a day before the analysis in order to allow the mixture to come to a "stable" status. Then, I use the mix as olvent.

But, of course, I have to decide what is better: fast disintegration, but contraction/temperature effects OR premix and long sonication times.

I will try how tedious the subsequent water - organic addition really is and then decide.

Regards

Florian

Florian, I understand your concern regarding temperature increase and that is why I sugested stepwise filling up to volume. The temperature equilibration would be an intermediate step, which could be shortened by cooling the solution/flask in water bath for instance.
Best regards