Measurement of Pharmaceutical Binders

The TriStar II with Krypton Option can measure materials with surface areas as low as 0.001 m2/g and is ideal for difficult-to­-measure pharmaceutical binders. Pharmaceutical binders such as microcrystalline methylcellulose (MMC), lactose, and gelatin typically have surfaces areas under 2 m2/g and, therefore, are perfect candidates for krypton adsorption with the Tristar II analyzer.

The Tristar II analyzer

Figure 1. The Tristar II analyzer

Advantages of Using Krypton

Isotherms are collected by measuring the amount of gas adsorbed by a material over a range of pressures at a constant temperature. The quantity of gas adsorbed by a material is determined by taking the original quantity of gas dosed into a tube (Vi) and subtracting the amount of gas remaining in the tube after equilibrium is reached (Ve).

For materials with low surface areas, the difference between the original amount of gas and the amount remaining after equilibrium (Vi – Ve) will be small and difficult to measure accurately, resulting in increased risk of error.

For materials with low surface areas, the amount of material is normally maximized in order to increase this difference (Vi – Ve). Unfortunately this approach has an upper limit depending on the size of the sample tube and the physical properties of the material. Another approach is to use an alternate analysis gas.

Krypton is an excellent choice for low surface area measurements. At 77 K, nitrogen has a saturation pressure of 760 torr, whereas krypton has a saturation pressure of only 2.5 torr. Since pressure is proportional to the number of moles or molecules in a set volume*, there are ~ 300 molecules of nitrogen for every 1 molecule of krypton. When the quantity adsorbed is significantly small, lowering the amount of molecules present by a factor of 300 substantially reduces the risk of error.

Analysis Parameters

USP method <846> Specific Surface is based on low-temperature gas adsorption and the BET surface area calculation. The relative pressure (P/Po) range used for the isotherms for this testing was restricted to 0.05 < P/Po < 0.15. USP <846> also calls for a correlation coefficient (or goodness of fit) larger than 0.9975.

All of the data presented meet this criteria:

Test amount ~ 0.3 g of each material
Preparation Degassed at ~ 40 °C for 48 hours, followed by degassing at 40 °C for two hours.
Free space Measured
Relative pressures 0.05 to 0.3 (results taken from 0.05 to 0.15)
Equilibration Relative pressure of 1.0 with an equilibration interval of 10s
Backfill Start of analysis only; not at conclusion

Experimental Results

The BET multipoint analysis was used to determine the surface areas of the three samples. The following table summarizes the results for all analyses:

Test Surface Area (m2/g)
MMC Lactose Gelatin
1 1.6398 0.7945 0.1319
2 1.6426 0.7767 0.1171
3 1.6245 0.7681 0.1132
4 1.6228 0.7597 0.1040
5 1.6185 0.7554 0.0987
6 1.5787 0.7488 0.0920
7 1.5989 0.7396 0.1076
8 1.5794 0.7348 0.0912
Average 1.6132 0.7597 0.1070
Standard Deviation 0.0249 0.0198 0.0137

Figure 2 shows plotted isotherms for one of the analyses.

Plotted isotherms for one of the tests

Figure 2. Plotted isotherms for one of the tests

This information has been sourced, reviewed and adapted from materials provided by Micromeritics Instrument Corporation.

For more information on this source, please visit Micromeritics Instrument Corporation.


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