Levothyroxine tabs

[michaelcarolus]

Hi All

I'm busy testing Levothyroxine tabs as per USP. The USP dissolution test has the following statement:
"Sample solution: Pass a portion of the solution under test through a suitable filter. [Note—Before use, check the filters for absorptive loss of drug. ]"
Could anyone recommend a suitable filter? We have tried a few filters but our data is inconclusive as to whether it is the filter or analytical method that is causing the problem.

Thanks in advance
Mike

[DoryFish]

Hi Mike,

I can't vouch for how reliable this info is (work done before my time), but I have a student thesis where Millex HV 33 mm 0.45 micron filters were used for dissolution studies of levothyroxine tabs.

Do hope this works - am about to repeat some of the work myself soon!

[michaelcarolus]

Thanks DoryFish

Looks like this is not an easy molecule to work with. The USP monograph has quite a few precautions in the dissolution test:
• [NOTE— All containers that are in contact with solutions containing levothyroxine sodium are to be made of glass.]
• [NOTE—Before use, check the filters for absorptive loss of drug.] – Dissolution Test 1
• [NOTE—Filter the Standard solution in a manner identical to the Sample solution.] - Dissolution Test 3
• [NOTE—Do not use paddle stirrers with synthetic coating.] - Dissolution Test 4
• Sample solution: Sample per Dissolution <711>. Centrifuge the solution under analysis. - Dissolution Test 4

I'm thinking of rather centrifuging the samples thereby eliminating the potential filter adsorption. I will need to establish suitable speed/time for centrifuging to prevent further dissolution while centrifuging.

Regards
Mike

[DoryFish]

Hi Mike,

We're sweating on the arrival of our 2014 version of the BP which will have a levothyroxine dissolution test for the first time. I'm therefore not sure what the requirements are.

After reading your comments, I had a look at the USP (USP29 which came up in google). Perhaps what I've pulled off the web isn't the correct version as it seems a bit odd. Tests 1, 2 and 3 all have the same medium and apparatus but different tolerances (ie. Q and time are: 70%/45 min, 80%/15 min and 80%/45 min). I can't see anything about coated tablets vs uncoated and why you'd have such different tolerates for the same experimental conditions.

Checking the filter type for adsorptive loss of drug and filtering standards and samples in the same manner is something we do for every drug. Don't understand why the USP Tests 1 and 2 have these as separate notes.

Should add I'm no expert so it doesn't take much to confuse me.

If the BP is worded similarly, we certainly won't be using Test method 4 since our paddles are coated.

[DoryFish]

Hi Mike,

The BP dissolution test is simple and straightforward. Apparatus 2, 100rpm, 37 oC and 500 mL water as dissolution medium. For tablets of 25 micrograms or less, add 2 tabs per dissolution vessel. Samples to be centrifuged.

Nothing to suggest the drug is difficult to work with.

Hope this info helps?

[michaelcarolus]

Morning All

Thanks so much for all your suggestions/comments. I'll definetely be proposing to centrifuge the samples.

Regards
Mike