Levothyroxine sodium loaded dissolving microneedle arrays for transdermal delivery

[helvella]

Have been waiting for this for, umm, years! Especially since many recent mentions of microneedle arrays for other medicines.

And suddenly fell across it today.

The idea that we just might have an option to avoid oral delivery of thyroid hormones is spectacularly great news. It might not be the best option for all. And cost, of course, might impose a severe limitation on availability.

ADMET DMPK. 2022 Sep 13;10(3):213-230.

doi: 10.5599/admet.1317. eCollection 2022.

Levothyroxine sodium loaded dissolving microneedle arrays for transdermal delivery

Riyam F Ghazi 1 , Mohammed H Al-Mayahy 1

Affiliations

• PMID: 36131889

• PMCID: PMC9484701

• DOI: 10.5599/admet.1317

Abstract

Levothyroxine (LT-4) sodium has shown variable bioavailability following oral administration. This can be assigned to the significant influence of gastrointestinal conditions, food and drugs administered concomitantly on the rate and extent of absorption from the gastrointestinal tract. Thus, the aim of this research study was to establish an efficient transdermal delivery system of LT-4 sodium via the application of hyaluronic acid dissolving microneedles. Microneedles-based drug delivery system consists of sharp-tip needles that puncture the top layers of the skin in a minimally invasive manner to create physical channels through which therapeutic molecules can easily diffuse into/across the skin. Hyaluronic acid polymer at different ratios (5-60 %) was used to prepare microneedle arrays (100 needles per array) using a micromoulding technique. Characterisation tests were carried out to select the optimum formulation. F11 formula containing 50% w/v hyaluronic acid and 1% v/v Tween 80 formula showed an appropriate needle shape with dimensions of 432 ± 6.4 μm in height and a tip diameter of 9.8 ± 1.3 μm. The microneedle arrays demonstrated a suitable mechanical strength after applying a force of 32 N per array and an excellent insertion ability both in Parafilm M® and human skin. The in vivo dissolution of microneedles was started rapidly within 5 minutes following the insertion in the skin and completed at 1 hour. Ex vivo permeation study using human skin has shown a significant improvement in LT-4 sodium delivery across the skin compared to control preparations (drug solution and microneedle free film). The microneedle array F11 has significantly (P ≤ 0.05) increased LT-4 sodium permeation through the skin (cumulative permeated amount of 32 ± 2 μg/cm2) in comparison to the control solution (cumulative permeated amount of 0.7 ± 0.07 μg/cm2) and the microneedle free film (cumulative permeated amount of 0.1 ± 0.02 μg/cm2) over 7 hours. The findings from the irritation test revealed that mild erythema was produced from the application of microneedle arrays which disappeared within 24 hours. Accordingly, dissolving hyaluronic acid microneedles could be a feasible and effective approach to delivering LT-4 sodium transdermally without causing significant skin damage.

Keywords: Hyaluronic acid; dissolving microneedles; levothyroxine sodium; micromoulding; transdermal delivery.

Full paper as PDF freely available here:

pub.iapchem.org/ojs/index.p...

[SlowDragon Administrator]

At last …..perhaps some progress

[Hidden]

Oh this is going to be a game changer! I’m in the US ( I couldn’t find a US group) I’m a bit worried how they will price this. My migraine meds are injectables and beyond ridiculous with the cost. Fingers crossed 🤞🏼 Thank you for the post!

[helvella Administrator Thyroid UK in reply to Hidden]

Always a major issue!

In the UK, levothyroxine tablets are extremely inexpensive. But liothyronine and levothyroxine oral solutions are expensive/very expensive.

[Regenallotment]

so is the next logical step advanced wearable sensors that identify our FT4 and FT3 levels and allow us to dose accordingly like diabetics? I suppose the timescales are different but the tech exists.

[StitchFairy in reply to Regenallotment]

Exactly what I've been wishing for, for years now. It would be amazing.

[helvella Administrator Thyroid UK in reply to Regenallotment]

I'm not convinced that the technology to measure FT4 and FT3 accurately, repeatedly and affordably by a sensor exists - either now or in the foreseeable future.

But that is not being negative. I do suspect that something could be detected and measured. Things that can act as proxies for thyroid hormones.

We currently have at least demonstration of sensors for temperature, blood pressure, photoplethysmograph (PPG) to measure blood volume pulse (BVP) and infer heart rate, oxygen saturation, electrodermal activity (EDA), sweat, phenylalanine (PHE), multiple movement sensors, electrocardiogram (ECG), red blood cell count, and respiratory rate.

For one example, the latest Apple Watch 8 adds temperature sensing.

The development of sensors has obviously continued and will go on increasing.

The development of the software to interpret those sensor readings will take years. And we'll likely see many annoyances such as the best set of sensors not all being available in one device! Especially when we might need to supply the context for the interpretation. A reduced body temperature in someone who is hypothyroid might require different logic as it has to include under-dosing as a possible cause.

[Charlie-Farley in reply to helvella]

Hi helvella 😊

As with everything if it is to be successful the medical profession will have to overcome the ‘hump’ with regards their understanding. Any test or instrument needs to be calibrated to the person, not the person to the test or instrumentation.

This is the big ‘gap’ at the moment that so many patients fall into by virtue of these diagnostic shortcomings. I mentioned similar on a diogenes string.

[helvella Administrator Thyroid UK in reply to Charlie-Farley]

Are you suggesting that our doctors are camels? 🐪🐫 🐫🐫🐪🐪

If we saw some sensor (or collection of sensors) that, intentionally or just by chance, correlated with thyroid health, and people actually had them by the million, I think it would impact treatment. But it could take a long time.

We might find that the vendors (Apple, FitBit, Garmin, etc.) notice things more readily than the medical establishment. Then, in a self-interested move, publishing could help spread the word and encourage take-up.

[Charlie-Farley in reply to helvella]

I would have more faith in techies to find imaginative solutions than doctors!

[birkie]

😆 In A&E waiting to be seen, I posted about that very thing sitting here with a 4 hour wait.. A lady who came in with a bad fall hadn't taken her insulin, she was taking in to a room to be given it... I just thought how convenient that would be for us... Just a injection of thyroid hormones we need, no tables sitting on our stomach waiting to be absorbed/converted.. No waiting an hour before eating or drinking.. 👍👍