Not 100%

[syx]

Dear members,
I have got a recovery problem when trying to determine active substance in tablets. Different solvent type and compositions have been tried and the result still low.

Solubility: slightly soluble in water and in 2-propanol, freely soluble in methanol, sparingly soluble in ethanol (BP). It is also soluble in dilute hydrochloric acid.

The latest solvent I have used is methanol : acetonitrile : 0.02N HCl (35:15:50). It is the composition of mobile phase, but the buffer is changed to HCl solution to increase solubility.

Finally, we made 3 kinds of ‘sample’ solutions:

1. A blend of placebo and active ingredient powder was transferred into a volumetric flask, and then the solvent was added.

2. The placebo and active ingredient were weighed separately, transferred into one volumetric flask, and then the solvent was added.

3. The active ingredient was transferred into a volumetric flask and dissolved with the solvent, and then the placebo was added before diluting up to volume with solvent.

As the result, sample 1 and 2 showed 95-96% recovery; and sample 3 gave approx 100%. Does anyone have any idea to overcome this case?

Best regards,
Siswanto Tanuatmojo

[Rob Burgess]

For sample 1, what are you basing your recovery calculations on i.e. how did you determine the level of within the belend to start with?
Sample 2 is giving odd results... is your active getting trapped somehow in the tablet placebo matrix I wonder?
Does the placebo matrix excipients dissolve fully?
You could try lengthing the extraction time i.e. shake / sonication steps.
Keep us posted if you can.... cheers

[ym3142]

SYX,
sorry, you have found a method giving 100% recovery which was perfect for you. Then what is your question?
Did you want to find a way to make all three methods give perfect recoery?

[syx]

Rob, the recovery sample (first sample) is a mixture of placebo and active substance as the formula of the tablets. There sample was prepared using 30 minutes sonication with frequent shaking. The active substance is very soluble in the solvent; we could see it when we do not add the excipients (placebo).

Ym, I could not get 100% recovery when trying to apply sample preparation to the recovery sample that I ever use in accuracy testing. Maybe as Rob said, there is something in the matrix that trapped the active substance and reduces its ‘solubility’. To ensure my hypothesis, I do the test to those 3 solutions. 100% is found only when we dissolve the active substance first and then add the placebo.

Do I need to prepare the standard solution with placebo addition?

[Consumer Products Guy]

I know lots of people like to match dissolution solvent to the mobile phase, and fully understand the advantages of such for samples nearer the detection limit, to minimize baseline disruptions. OK, I never work with tablets, but assume that in sample preparation you pulverize them and then weigh out your sample. So assuming that you don't NEED to use mobile phase as dissolution solvent, I personally would use methanol as the solvent as the sought-for substance freely dissolves in it. Who cares if the excipients dissolve, not me. I'd keep the injection volume relatively small as the dissolution solvent methanol is "stronger" than your mobile phase which contains 50% aqueous. Hey, we're scientists, our job is to try things, that's what I'd try.

[syx]

I have tried methanol and got same result.

[A.Nonymous]

Maybe your excipiens are forming some micelles, which adsorb your API.

Perhaps its one component of you matrix which is absorbing your API, so you can find out which one it is.

Maybe a stupid question: did you do the test only one time or do you have repeated the procedure to ensure it is really absorbing?


Good luck

[syx]

The procedures were repeated and the results confused me...
Do you have any idea about other possible cause?

[A.Nonymous]

You have repeated your tests and the results confused you?
If I understand well, your results aren't giving you the same results as stated before.

Then the first thing to do is to repeat your analysis until you are sure of your results. It's possible that there is a lot of variation on your method, and your results arent't that consequent.

If this is the case, you should primary work on your method precision and then secondary on your method recovery.

Good Luck

[gbalock]

SYX,
You don't say what your API or excipient matrix are. Is it possible that you have an excipient/drug interaction? That would be one explanation of your recovery issue.
George

[syx]

The placebo could not be dispersed in the solution as fine particles. They formed something like wads of cotton. Maybe I need to ask our formulator about the excipients.

[A.Nonymous]

SYX,
You don't say what your API or excipient matrix are. Is it possible that you have an excipient/drug interaction? That would be one explanation of your recovery issue.
George

George, how do you explain that it only happens when the API and excipiens are mixed dry and not when mixed dissolved?