Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems-Instrumental Screening

[helvella]

This is the sort of study that should have been done years ago. (At least, to the extent that the analytical techniques of the day were sensitive enough). And repeated as new analytical techniques became available.

The sentence below, taken from the conclusions, is so obvious it is frightening that any of the intended audience of medically and scientifically trained persons could possibly need it pointed out to them. Let us hope it is an excess of caution and stating the bleeding obvious.

Since the amount of levothyroxine in solid formulations (tablets) is considerably lower in comparison to the amount of excipients (even 1000 fold lower), the interactions that could occur can lead to a drastic diminution of therapeutic activity, i.e., bioavailability.

Pharmaceutics. 2020 Jan 10;12(1). pii: E58. doi: 10.3390/pharmaceutics12010058.

Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems-Instrumental Screening.

Ledeți I1, Romanescu M1, Cîrcioban D1, Ledeți A1, Vlase G2, Vlase T2, Suciu O3, Murariu M4, Olariu S4, Matusz P5, Buda V6, Piciu D7,8.

Author information

Abstract

The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the inducing of interactions during thermal stress. The corroboration of instrumental results led to the conclusion that LTSS is incompatible with lactose, mannitol and sorbitol, and these excipients should not be considered in the development of new generic solid formulations.

KEYWORDS:

excipient; instrumental analysis; levothyroxine sodium; preformulation study

PMID: 31936742

DOI: 10.3390/pharmaceutics12010058

ncbi.nlm.nih.gov/pubmed/319...

Full paper freely accessible here:

mdpi.com/1999-4923/12/1/58

[Hidden]

Very interesting! After trying a few different brands of Levo with no apparent ill effects I thought I was OK with all of them.

Shall have to start examining the ingredients in different brands!

[helvella Administrator Thyroid UK in reply to Hidden]

When I started levothyroxine, despite knowing that people had different opinions, I was determined that it would make no difference to me.

Old formula Teva, the one that was taken off the market in 2013 for being effectively sub-potent, removed the possibility of continuing to believe that.

I then realised the differences between Actavis and Mercury Pharma were significant.

So far, my favourites have been L-Thyroxin Henning - from Germany - and UniPharma - from Greece. But I am OK on Actavis (100) plus Mercury Pharma (25).

[sy28]

malpractice comes to mind ... doesn't it explain what we've long suspected. this is helpful, thank you.

[crimple]

Thank you for posting Helvella, very interesting. At least I am now quite certain that it is not an overactive imagination which leads me to having specific requirements! I can only tolerate Actavis levo, Mercury gave me severe gastric symptoms.

Has similar research been conducted with Liothyronine( T3)?

I have just been allowed to have an NHS T3 scrip and had to tell the pharmacy that I would not be able to tolerate Morningside and Mercury Pharma because of acacia powder. Due to 2012 Teva debacle I will never trust that brand, so they have to find me Sigma Pharma, which is about £400 each month!!

I appreciate that the research into fillers is about the ability for the levo to be used effectively and that is different to personal intolerances to some of the fillers.

It seems with respect to Fillers that just about anything can be used as long as they are not designated poisons!!

Keep up the good research.

[helvella Administrator Thyroid UK]

As the risk of repeating what I and the paper have already said...

Some excipients (inactive ingredients) of levothyroxine tablets - lactose, mannitol and sorbitol - are seen to react with levothyroxine. We need to understand what those reactions are and what substances are produced.

There are many other medicines which contain these excipients but do not seem to cause the same sort of issue we hear about from levothyroxine products. If the levothyroxine reacts with one or more excipients, it could well form substances which have never been properly identified and investigated.

(Of course, some people react badly to lactose in any form and from any source.)

[helvella Administrator Thyroid UK]

As we have had quite lot of posts specifically mentioning mannitol and/or lactose recently, I thought I would add a response on this thread so it will re-appear in members' news feeds.