[dun13203171]

Hi guys,
           I did a project where I tested the dissolution of aspirin at different pH's.

I made a serial dilution, read the absorbances and plotting conc/absorbance.

From this calibration curve I was able to read my absorbances from my main experiment and plot various graphs showing concentration over time.

My question is, how could I calculate percentage of dissolved active ingredient/time?

Concentration of sample at specific interval
______________________________________           x 100

total concentration of active ingredient in tablet



All input appreciated, the project is almost finish, 95% of it is written up, I have to submit this on tuesday and would like to add some graphs of percentage of dissolved active ingredient/time


thanks in advance

[dun13203171]

I was thinking of dissolving my tablet in say 5ml of water, taking a 1ml sample, placing it in a cuvette, complexing it with iron chloride, reading the absorbance, using the calibration graph done previously for the concentration and multiplying it by 5 for the total concentration of the tablet.

Does this sound ok?

[Arkcon]

All my enteric coated tablet data sets came out great for pH2, pH8 and when in a control, just what was expected.

But for a dispersible tablet with the same mg of aspirin in it, the absorbances/conc are much lower at pH8 and in the control in comparison to the enteric coated which doesn't seem to make sense as since they are disperible I would have thought they would have been very high, or close tothe same as enteric coated.

Do you know why, since its disperible could it be degrading very quickly?

Possibly.  Also, pH may be interfering with your assay, its probably meant to be run at a certain pH, and your acid and base samples may be overloading sample conditions, you'll have to see how your assay works.  Also, don't discount that the pH difference may alter the spec response of the molecule.

[pgk]

Tablet dissolution follows the Noyes-Whitney equation:
dC/dt = k(Co – C)
Where, C is the concentration of sample at a specific interval t,
Co is the total concentration of active ingredient in the tablet,
k is the dissolution constant.
By transforming to:
dC/(Co-C) = kdt
followed by integration of both sides, you get:
C = Coexp(1- kt)
So, you can calculate the desired percentage.
k can be calculate by replacing C/Co  = 0.5 and the corresponding interval t½, from your plots.
Aspirin is a weak acid and thus, Co is equal with sum of ionized and unionized form:
[Co] = [HA] + [A-]
By replacing that to acid dissociation constant equation, you get the influence of pH, in the Noyes-Whitney equation (the dissociation constant of aspirin is known).
PS: Experimental values might be slightly different than the theoretical ones, due to the excipients interference to the dissolution.

[dun13203171]

All my enteric coated tablet data sets came out great for pH2, pH8 and when in a control, just what was expected.

But for a dispersible tablet with the same mg of aspirin in it, the absorbances/conc are much lower at pH8 and in the control in comparison to the enteric coated which doesn't seem to make sense as since they are disperible I would have thought they would have been very high, or close tothe same as enteric coated.

Do you know why, since its disperible could it be degrading very quickly?

Possibly.  Also, pH may be interfering with your assay, its probably meant to be run at a certain pH, and your acid and base samples may be overloading sample conditions, you'll have to see how your assay works.  Also, don't discount that the pH difference may alter the spec response of the molecule.

The degreadation of the dispersible aspirin is a possibility!

Do you know of any decent articles which may go into the science of how pH could interfer with an assay?

I have been given until tomorrow to get this in, so I just need to give some reason why the dispersible sets may not have worked and the science behind these reasons.

Many thanks akcon

and many thanks pgk!

[pgk]

Aspirin is a weak acid and thus and in the acqueous dissolution medium, it is dissociated by the following way:
HA → H+ + A-
with a dissociation constant, which is equal to:
Ka = ([H+][A-])/[HA]
The initial concentration Co in the tablet, is equal to the unionized form [HA] but during dissolution (after tablet wetting), [Co] is equal to the sum of concentrations of both ionized and non-ionized forms:
[Co] = [HA] + [A-]
By replacing the above equivalence, in the dissociation constant equation, we get:
[Co] = [HA] + [HA]Ka/[H+] = [HA](1 + Ka/[H+]) =  Co(1 + Ka/[H+]) 
and replacing the overall, in the Noyes–Whitney equation, we get:
dC/dt = k[Co(1 + Ka/[H+]) - C)]
Silly question: What is the relationship between [H+] and pH?