Excipient Characterization Using Krypton Adsorption and BET Modeling

The Guggenheim, Anderson, and de Boer (GAB) equation is an extensively referenced model often used for characterizing excipients, pharmaceuticals and food.

BET modeling and krypton adsorption can be used to find the water sorption, as-received surface area, and krypton sorption to determine the impact of water sorption on the BET surface area.

The BET equation is normally applied to nitrogen adsorption isotherms and a narrow range of data (0.05 < p/p° < 0.30), whereas the GAB equation may be applied to water adsorption isotherms and is suitable for a broad range of data (0.05 < a° < 0.90 ).

For water sorption studies, the term activity is used rather than relative pressure and therefore a° = p/p°. This is the same convention for water adsorption isotherms, to remain consistent with the application and previously published articles.

Experimental Procedure

Spectrum offers three commercially available excipients - lactose, gelatin and talc. Simple degassing was used to prepare each sample in a vacuum at room temperature overnight.  To avoid morphological changes, the samples were not heated.

The Micromeritics 3Flex surface characterization analyzer was used to measure the krypton adsorption isotherms after degassing. The surface area analyses and measurements of each excipient were conducted in a parallel hi-speed mode using Kr adsorption isotherms.

The samples were degassed again using the previously described technique on completion of the krypton adsorption measurements. Water adsorption isotherms were collected for each excipient using the Micromeritics 3Flex analyzer on completion of the preparation.

In similar manner as the krypton analysis, the water adsorption isotherms were collected in a parallel manner and the adsorption isotherms are given in Figure 1.

Water adsorption isotherms measured at room temperature for gelatin, lactose, and talc.

Figure 1. Water adsorption isotherms measured at room temperature for gelatin, lactose, and talc.

Re-degassing of the excipients was done and krypton adsorption was used to determine the surface area of the excipients after exposure to water.

Data Analysis

MicroActive software for the 3Flex analyzer was used for the water adsorption and krypton isotherms. BET surface area was calculated using the krypton adsorption data for the as-received excipients and the post-water sorption samples. Using the isotherm data over the range of 0.05 - 0.15 relative pressure ( p/p°), the BET surface area was calculated.

GAB Equation

BET Equation

Bothe the GAB and BET equations were used to analyze the water adsorption isotherms to determine monolayer capacities for water. Advanced reporting capabilities using the Python programming language is featured in the MicroActive software. The analysis of water adsorption isotherms was done using two simple python scripts.

The quantity adsorbed in mmoles/g was converted to mg/g of the sample in the first script. Though this calculation is trivial, it is a convenience that offers reporting flexibility and enables users to compare high-quality isotherm data with results obtained from micro balances.

The second python script was used to determine the GAB parameters for each excipient. The MicroActive software and the use of Python scripting offers user flexibility to add advanced reporting options and make these calculations part of their standard reporting practices.

Table 1 lists the BET and GAB parameters for the water adsorption isotherms. The results from the krypton adsorption analyses show that the BET surface area of gelatin was reduced 20%, lactose was reduced 4%, and there was no change in the talc after exposure to water.

Table 1. Summary of BET surface area results (1 and 3) from krypton sorption isotherms and gab and bet parameters derived from water adsorption isotherms (2). The BET surface area was determined using krypton adsorption for the as-received excipients (1) and after collecting the water adsorption isotherms (3).

Adsorptive Krypton (1) Water (2) Krypton (3)
Analysis BET GAB BET BET
Surface Area Pore volume nm C k nm C Surface Area
m2/g ml/g mg/g mg/g m2/g
Gelatin 0.12 0.194 104.9 15.6 0.653 66.3 16.3 0.096
Lactose 0.53 0.003 2.0 907.5 0.199 1.8 148.3 0.51
Talc 7.58 0.005 1.1 82.7 0.794 1.0 66.1 7.58

The parameters calculated from the water adsorption isotherms are consistent with previous reports comparing the GAB and BET equations. For all three excipients the monolayer capacity calculated using the GAB equation exceeded the values obtained from the BET equation.

It is interesting to note that the BET model was applied to the activity ranging from 0.05 to 0.3 while the GAB equation was used to model the activity over a broader range from 0.05 to 0.8, Figure 2.

Figure 2. GAB model (line) for water adsorption isotherms for Gelatin, Lactose, and Talc.

Conclusions

The Micromeritics 3Flex adsorption analyzer offers a characterization platform for determining the adsorption isotherms of a wide range of probe molecules. In this study, krypton is used to precisely determine the surface area of pharmaceutical excipients.

The 3Flec was employed to determine the water uptake of these excipients over a broad range of activity. The use of krypton adsorption shows the utility of these complicated experiments of measuring the surface area both before and after exposure to water.

A main feature of the protocol is the in-situ handling of the excipients. After the sample was loaded and connected to the 3Flex analyses was done without removing the cell from the instrument. The parallel analyses and 3Flex ensured that the samples were not contaminated during transport or handling to obtain the isotherm data.

For 3Flex software, the python programming language has been incorporated into the MicroActive and this powerful scripting language allows users to develop extensions to the standard report library available within the 3Flex application. The use of python helped in implementing new models like the GAB equation or helped in expressing the adsorption data as mass of water absorbed in a rapid manner. The Micromeritics 3Flex provides a flexible and extensible platform for material characterization.

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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