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Measuring the specific surface area (SSA) of freeze-dried biologics using inverse gas chromatography.
Eur J Pharm Biopharm. 2019 Sep; 142:216-221.EJ

Abstract

The specific surface area (SSA) of freeze-dried biologics (FD) is usually measured via a Brunauer-Emmett-Teller (BET) analysis of volumetric nitrogen adsorption isotherms. However, this technique has accuracy limitations for materials <0.5 m2/g, requires dry samples, must be measured at 77 K and has slow sample preparation times (drying/degassing). Inverse gas chromatography (IGC) is chromatographic characterization technique which can be used to analyse the SSA (down to ≈0.1 m2/g) of various solid-state materials including powders using organic molecules such as octane at ambient temperatures/pressure for a range of relative humidities. This study presents a comprehensive comparison between the N2 BET adsorption versus octane BET adsorption using IGC methods for determining the SSA's for a range of freeze dried biological materials. These include IgG 5% w/w, an influenza antigen standard, sucrose 5% w/w and trehalose 5% w/w. IGC provided comparable SSA values to the N2 BET method with better reproducibility (lower RSDs %). Large variations in average SSA within manufactured FD batches were observed for both IGC and volumetric determinations. IGC was also used to measure the change in SSA with increasing humidity, with FD cakes shrinking and losing their structural integrity with increasing moisture content. Such information highlights the importance of moisture content in determining the physical stability of FD cakes as exemplified by their SSA. In conclusion, IGC is a suitable alternative method for determining the SSA of freeze-dried biological materials which are generally strongly dependent on their moisture content.

Authors+Show Affiliations

Surfaces and Particle Engineering Laboratory, Department of Chemical Engineering, Imperial College London, SW7 2AZ, United Kingdom.National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom.Surfaces and Particle Engineering Laboratory, Department of Chemical Engineering, Imperial College London, SW7 2AZ, United Kingdom. Electronic address: d.r.williams@imperial.ac.uk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31233863

Citation

Duralliu, Arnold, et al. "Measuring the Specific Surface Area (SSA) of Freeze-dried Biologics Using Inverse Gas Chromatography." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 142, 2019, pp. 216-221.
Duralliu A, Matejtschuk P, Williams DR. Measuring the specific surface area (SSA) of freeze-dried biologics using inverse gas chromatography. Eur J Pharm Biopharm. 2019;142:216-221.
Duralliu, A., Matejtschuk, P., & Williams, D. R. (2019). Measuring the specific surface area (SSA) of freeze-dried biologics using inverse gas chromatography. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 142, 216-221. https://doi.org/10.1016/j.ejpb.2019.06.026
Duralliu A, Matejtschuk P, Williams DR. Measuring the Specific Surface Area (SSA) of Freeze-dried Biologics Using Inverse Gas Chromatography. Eur J Pharm Biopharm. 2019;142:216-221. PubMed PMID: 31233863.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Measuring the specific surface area (SSA) of freeze-dried biologics using inverse gas chromatography. AU - Duralliu,Arnold, AU - Matejtschuk,Paul, AU - Williams,Daryl R, Y1 - 2019/06/22/ PY - 2019/04/30/received PY - 2019/06/17/revised PY - 2019/06/21/accepted PY - 2019/6/25/pubmed PY - 2019/11/26/medline PY - 2019/6/25/entrez KW - BET KW - Biologics KW - Freeze-drying KW - Inverse Gas Chromatography (IGC) KW - Moisture content KW - Specific Surface Area (SSA) SP - 216 EP - 221 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 142 N2 - The specific surface area (SSA) of freeze-dried biologics (FD) is usually measured via a Brunauer-Emmett-Teller (BET) analysis of volumetric nitrogen adsorption isotherms. However, this technique has accuracy limitations for materials <0.5 m2/g, requires dry samples, must be measured at 77 K and has slow sample preparation times (drying/degassing). Inverse gas chromatography (IGC) is chromatographic characterization technique which can be used to analyse the SSA (down to ≈0.1 m2/g) of various solid-state materials including powders using organic molecules such as octane at ambient temperatures/pressure for a range of relative humidities. This study presents a comprehensive comparison between the N2 BET adsorption versus octane BET adsorption using IGC methods for determining the SSA's for a range of freeze dried biological materials. These include IgG 5% w/w, an influenza antigen standard, sucrose 5% w/w and trehalose 5% w/w. IGC provided comparable SSA values to the N2 BET method with better reproducibility (lower RSDs %). Large variations in average SSA within manufactured FD batches were observed for both IGC and volumetric determinations. IGC was also used to measure the change in SSA with increasing humidity, with FD cakes shrinking and losing their structural integrity with increasing moisture content. Such information highlights the importance of moisture content in determining the physical stability of FD cakes as exemplified by their SSA. In conclusion, IGC is a suitable alternative method for determining the SSA of freeze-dried biological materials which are generally strongly dependent on their moisture content. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/31233863/Measuring_the_specific_surface_area_(SSA)_of_freeze-dried_biologics_using_inverse_gas_chromatography L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(19)30384-4 DB - PRIME DP - Unbound Medicine ER -