Tablet splitting of a narrow therapeutic index drug: a case with levothyroxine sodium

This impact was minimized by chemometrics preprocessing step including multiplicative signal correction (normalization). The color index indicates that the region rich in levothyroxine concentration is red whereas regions with minimum levothyroxine are blue in color. It was observed that L-2 and L-4 tablets’ surfaces showed heterogeneity in the distribution of API as compared to other marketed tablets. A more careful evaluation at the composition of tablets from the package insert revealed that these formulations might be compressed directly without any granulation step since there was no binder present in both these formulations. API% is very low in the tablet (200mcg in 120 mg tablet ~0.167%); hence, if the API is mixed directly with other ingredients without formation of granules, it seems likely that the drug will not be homogeneously mixed with the other ingredients.

Key concern 3: chemical instability

This question, frequently pondered by those managing thyroid conditions, requires careful consideration. While seemingly a simple solution for adjusting dosage, splitting thyroid medication tablets can introduce significant risks and uncertainties regarding consistent absorption and overall treatment efficacy. Understanding the potential consequences is crucial for maintaining optimal thyroid health and preventing unforeseen complications. However, of the 16 studied medications identified, only digoxin degraded fast enough for chemical instability to be considered clinically important. Where medications are known to degrade, or where there is uncertainty, splitting only one tablet at a time should mitigate this concern. No studies were found examining bioavailability after enteric coated tablets were split.

Samples were stored in monitored environmental chambers (Hotpack, Philadelphia, PA or Electrotech, Glenside, PA) under long-term storage conditions (25°C/60% relative humidity (RH)) for 8 weeks. On the appropriate time points (0, 4, and 8 weeks), the closed pharmacy vials were removed from the incubators and allowed to equilibrate at room conditions for at least 1 h. At 0 week time point, the samples were also analyzed for weight variation, content uniformity (CU), and dissolution. Also near infrared (NIR) chemical imaging was used to visualize the contents of the surface of the whole tablets. In the authors’ experience, pharmaceutical representatives commonly discourage the splitting of their products.

Key concern 4: weight/dose variability

The pure component spectra were used to create a spectral library against which each tablets’ spectra were analyzed. CU determination for tablet samples was performed by grinding 10 whole tablets or split portions individually followed by quantitatively transferring them into individual volumetric flasks for subsequent CU experiments. That’s because the higher dose is frequently priced about the same as the lower dose.

Tirosint-SOL’s extensive dosing options provide clinicians with more choices, enabling them to adapt levothyroxine therapy to individual needs and better treat the full spectrum of hypothyroid patients. Increased dosage flexibility may also eliminate or reduce the need to change patients’ doses. Altering thyroid medication dosage should always be discussed with your doctor; never cut pills in half without professional guidance. Sometimes, focusing on aesthetics can help with overall well-being; for instance, if you’re concerned about teeth discoloration, you might find helpful information on how to address this at how to get rid of brown spots on teeth.

• This study was done to compare the performance of using 1.5 tablets of 100 μg Levothyroxine and the simultaneous using of one 100 and one 50 μg tablets in patients with DTC.
• A PLS-2 model was developed based on the spectral library of pure components and was applied to each tablet.
• Nevertheless, if this is your preferred method, use a very little amount of water (10-15 mL, or around one tablespoon), mix the powder in the water, and drink.

The standards were then transferred to an automatic injector for HPLC analysis. Levothyroxine tablet is cited as one of the drug products that could be safely split to cut the cost (14). However, it is a drug recognized to have a narrow toxic to therapeutic ratio with significant clinical consequences of excessive or inadequate treatment. There are 12 available tablet strengths of levothyroxine that vary by as little as 9% in drug content, reflecting the close titration that is required for optimal patient management. Thirteen million Americans are on levothyroxine products and those especially susceptible to incorrect titration include the elderly, pregnant women, their developing fetuses, and those with thyroid cancer (15).

As the primary interest was in gathering and synthesising both opinion and non-clinical trial research related to tablet splitting, the usual PRISMA processes for evaluating study quality (which focus on clinical trials) did not apply. Sapphire® chemical imaging system (Malvern, Westborough, MA) with SapphireGo® data acquisition system (version 1.4) equipped with diffuse reflectance detector was used to collect NIR spectra from 1,400 to 2,350nm in 10 nm increments. Background signal was removed initially by subtracting a dark cube without any sample. Spectralon-99% was used as a reflectance standard which is nominally 99% reflectant over the 350–2500 nm range. Each sample spectra is then recorded as a ratio of the specimen reflectance and the source light reflected from a Spectralon 99%.

Since assay is a composite test, content uniformity was also performed for all the split portions and was compared with whole tablets (Table I). Since content uniformity failed for L-4 whole tablets, split portions also failed to have levothyroxine content within the specifications. A higher fragmentation was observed for tablets cut with the splitter as compared to those cut with the hand (Fig. 2), and this might be the reason for the higher failures observed for the splitter cut portions. Dissolution on whole and split tablets was performed, and the results were in line with content uniformity, i.e., for split portions, some of the tablets failed to meet the USP specification as compared to whole tablets (Table II).

Publication types

Tablet splitting is a practice often recommended by healthcare providers and implemented by healthcare systems aimed at reducing the cost of prescriptions. An FDA study found that the thyroid drug levothyroxine should not be cut even when tablets are scored (AAPS PharmSciTech, Sept., 2010). Tablets of the brand-name drug Synthroid are scored, but synthroid sleeplessness this is considered a dose-critical drug. So variation in dose caused by uneven pill breakage could pose problems for patients.

I am wondering whether it could possibly be that I don’t tolerate the Teva band of Levothyroxine very well as this all started up when I changed brands. They dissolve very quickly so be sure to have a full glass of water so they don’t stay in the throat. The Levothyroxine consumption pattern was unchanged in both groups at the first and at the end of the study. The mean time interval between two assessments was 78.5 (26 to 175 days) with the standard deviation of 33.6.