Using Gravimetric Loss on Ignition Analysis to Determine Residue on Ignition (ROI) in Pharmaceutical and Nutraceutical Products

Nutraceutical and pharmaceutical drugs often contain two key components such as excipients and active pharmaceutical ingredients (APIs). Excipients are synthetic or natural fillers that are used to increase volume or mass, color and flavor to the drug’s delivery system. Certain excipients can also help extend the shelf life of drugs and may aid in absorption into the body.

APIs are used as major ingredients in tablets, capsules and medicinal powders, which are used for treating or preventing diseases. When compared to excipients, APIs have low concentration level and thus make it complex to develop drugs at consistent levels (Figure 1).

Grains of salt simulate 500mcg of API compared to tablet mass

Figure 1. Grains of salt simulate 500mcg of API compared to tablet mass.

To this end, the United States Pharmacopeia (USP) and the Food and Drug Administration (FDA) have issued many guidelines and protocols to ensure consistency in drug dosage. One such USP method (USP 281) is Residue on Ignition (ROI), which is designed to determine the amounts of inorganic components of either the API, excipients or both in pharmaceutical or nutraceutical drugs. These components comprise mineral salts and other trace metals which are left behind when the product is incinerated in a muffle furnace for a number of hours.

A gravimetric Loss on Ignition instrument is designed to achieve a 600°C temperature and enables operators to simulate the temperatures of a muffle furnace sans any preparation, run time, or cool down period.

The Computrac® MAX® 5000XL Instrument (Figure 2) combines a four decimal place digital balance with the temperature performance of a muffle furnace, thus enabling operators to test for % ROI and examine a product’s percent moisture at reduced temperatures.

Further functions such as data acquisition from web server, slow ramp temperature scans, and linked test capability can serve as useful tools when validating or optimizing the chemical composition of the end product.

Computrac® MAX® 5000XL moisture & ash analyzer.

Figure 2. Computrac® MAX® 5000XL moisture & ash analyzer.

A traditional oven and muffle furnace protocols were used as references to measure the ROI and percent moisture from vitamins and supplements and the results obtained were compared to samples tested by the MAX® 5000XL Instrument. All these drugs were grocery products which comprised Red Yeast Rice Powder and Vitamin B12, C, and D.

Results and Discussion

Moisture Results

It is important to monitor moisture content during and after the formulation of end product. This procedure helps detect problematic batches and thus saves significant amount of time and money and also ensures the wellbeing of end users. References and MAX® 5000XL were carried out in triplicate. Both MAX® 5000XL and oven references were run with 3g of powdered sample at 100°C for a period of 1h.

Figure 3 shows error bars plotted to denote one standard deviation below and above the mean of each data set. This data shows the equivalence between the standard oven method and the MAX® 5000XL method.

For all supplements, each set of data falls within the margin of error of the corresponding oven mean. The mean test time for each set of samples is shown in Figure 3b. When compared to the standard oven reference, test times are relatively shorter on the MAX® 5000XL.

Error bars

Figure 3. Error bars plotted to represent one standard deviation above and below the mean of each data set.

Table 1. Averaged test times of the oven reference and the MAX® 5000XL.

% Moisture Vitamins Averaged Test Times (min)
Oven MAX 5000XL
B12 60:00 6:32
C 60:00 4:16
D 60:00 4:32
Red Yeast 60:00 8:54

Residue on Ignition Results

In case both ROI and moisture testing have to be carried out on the same sample, a 1-hour test have to be performed in the oven at 100°C, and the same set of samples must be linked to a 2-hour furnace method at 600°C.

On the other hand, the MAX® 5000XL is capable of joining multiple tests on the same sample. This means, more date can be collected in a shorter period of time sans operator interference. The instrument also enables operators to determine Dry % ROI or Total % ROI within a range of linked tests.

Error bars are plotted to denote one standard deviation below and above and the average of each set of data set (Figure 4). This data shows the equivalence between the muffle furnace method and the MAX® 5000XL method. For all vitamin and supplements, each set of data is ± the standard deviation of the corresponding muffle furnace. Figure 4b shows the averaged test times of the muffle furnace and the MAX® 5000XL.

%ROI (@600 C)

Figure 4. Error bars plotted to represent one standard deviation above and below the mean of each data set.

Table 2. Averaged test times of the muffle furnace and the MAX® 5000XL.

% ROI Averaged Test Times (min)
Muffle Furnace MAX 5000XL
B12 120:00 16:48
C 120:00 20:22
D 120:00 15:12
Red Yeast 120:00 16:58

In addition to ROI and moisture analysis, the MAX® 5000XL instrument enables operators to control temperature with a resolution of 1°C/min. Although these temperature scans may take longer than the usual ROI tests, they enable individual volatiles to evolve from the sample at varied temperatures. Upon scanning the four drugs from 50°C to 600°C at a rate of 5°C/min, the ensuing graphs were created, as shown in Figures 5a and 5b.

% ROI scan for all four vitamins and supplements.

Figure 5a. % ROI scan for all four vitamins and supplements.

Rate profile during temperature scan.

Figure 5b. Rate profile during temperature scan.

Figure 5a shows that the % ROI scan for all four vitamins and supplements display different thermal profiles, and Figure 5a shows the rate profile during this temperature scan.

The red yeast rice powder has very few excipients. The thermal profile shows this purity as only two main peaks are seen: API (red yeast rice powder) peak at 300°C and moisture peak at 80°C.

While these rate profiles provide a better understanding about the chemical composition of these vitamins, they do not describe a particular chemical species. Additional study may have to be carried out to interpret this data from the thermal profile.

Conclusion

Nutraceutical and pharmaceutical firms should ensure that the drugs they distribute are safe, effective, and consistent between different batches and production. USP and FDA regulations should be taken into account during and after the formulation of end products. This includes determining the ROI of the APIs and excipients.

AMETEK Brookfield Arizona has shown the equivalence between the Computrac® MAX® 5000XL analyzer and the muffle furnace method for vitamins and supplements. This instrument has included the elements of a four decimal place digital balance, TGA instrument, muffle furnace, and standard oven to produce results that are both precise and reproducible. Thus, the MAX® 5000XL is an excellent analytical tool for pharma/nutraceutical products.

Arizona Instrument

This information has been sourced, reviewed and adapted from materials provided by AMETEK Brookfield Arizona

For more information on this source, please visit AMETEK Brookfield Arizona

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