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Determination of BET Specific Surface Area of Hydrate-Anhydrate Systems Susceptible to Phase Transformation Using Inverse Gas Chromatography

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Abstract

Specific surface area (SSA) is an important parameter in drug development that affects other downstream pharmaceutical properties of interest such as reactivity, stability, dissolution, and ultimately bioavailability. Traditionally, the Brunauer–Emmett–Teller (BET) SSA of pharmaceutical powders is measured via gas adsorption (nitrogen or krypton) that is preceded by a prolonged degassing step under low pressure. This degassing step may not be suitable for certain pharmaceutical hydrates that are susceptible to dehydration and phase transformation under reduced pressure and humidity conditions. Therefore, inverse gas chromatography (IGC) was explored as a reliable alternate technique for determining the SSA of model anhydrate–hydrate systems (trehalose and thiamine hydrochloride) that are prone to such phase transformation during SSA measurement. Both trehalose dihydrate and thiamine HCl non-stoichiometric hydrate were found to undergo partial phase transformation to anhydrous forms during BET analysis via degassing and gas adsorption. In contrast, these hydrates remained stable during surface area analysis using IGC owing to measurements under controlled relative humidity. Thus, IGC proved to be a viable technique for SSA measurement of pharmaceutical hydrates without compromising their physical stability.

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References

  1. Zielinkski JM, Kettle L. Pharmaceutical physical characterization: surface area and porosity. Intertek Pharmaceutical Services. 2013.

  2. Duffin R, Tran C, Clouter A, Brown D, MacNee W, Stone V, et al. The importance of surface area and specific reactivity in the acute pulmonary inflammatory response to particles. Ann Occup Hyg. 2002;46(suppl_1):242–5.

    Google Scholar 

  3. Byrn SR, Zografi G, Chen XS. Solid state properties of pharmaceutical materials, first. Hoboken, NJ: John Wiley & Sons; 2017.

    Book  Google Scholar 

  4. Carpin M, Bertelsen H, Dalberg A, Bech J, Risbo J, Schuck P, et al. How does particle size influence caking in lactose powder? J Food Eng. 2017;209:61–7.

    Article  CAS  Google Scholar 

  5. Garg V, Mallick S, García-Trinanes P, Berry RJ. An investigation into the flowability of fine powders used in pharmaceutical industries. Powder Technol. 2018;336:375–82.

    Article  CAS  Google Scholar 

  6. Blagden N, de Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev. 2007;59(7):617–30.

    Article  CAS  Google Scholar 

  7. Vippagunta RR, Pan C, Vakil R, Meda V, Vivilecchia R, Motto M. Application of surface area measurement for identifying the source of batch-to-batch variation in processability. Pharm Dev Technol. 2009;14(5):492–8. https://doi.org/10.1080/10837450902763007.

    Article  CAS  PubMed  Google Scholar 

  8. Zeng X. Solid state characterization of pharmaceuticals. Hoboken, NJ: Blackwell Publishing Ltd; 2011.

    Google Scholar 

  9. Carstensen JT. Pharmaceutical principles of solid dosage forms. Lancaster, PA: Technomic Publishing Company Inc.; 1993.

    Google Scholar 

  10. Brunauer S, Emmett PH, Teller E. Adsorption of gases in multimolecular layers. J Am Chem Soc. 1938;60(2):309–19. https://doi.org/10.1021/ja01269a023.

    Article  CAS  Google Scholar 

  11. Zhou QT, Denman JA, Gengenbach T, Das S, Qu L, Zhang H, et al. Characterization of the surface properties of a model pharmaceutical fine powder modified with a pharmaceutical lubricant to improve flow via a mechanical dry coating approach. J Pharm Sci. 2011;100(8):3421–30.

    Article  CAS  Google Scholar 

  12. Kondor A, Santmarti A, Mautner A, Williams D, Bismarck A, Lee K-Y. On the BET surface area of nanocellulose determined using volumetric, gravimetric and chromatographic adsorption methods. Frontiers. Chem Eng. 2021;3. https://doi.org/10.3389/fceng.2021.738995.

  13. Phadke DS, Collier JL. Effect of degassing temperature on the specific surface area and other physical properties of magnesium stearate. Drug Dev Ind Pharm. 1994;20(5):853–8. https://doi.org/10.3109/03639049409038335.

    Article  CAS  Google Scholar 

  14. Lapham DP, Lapham JL. Gas adsorption on commercial magnesium stearate: effects of degassing conditions on nitrogen BET surface area and isotherm characteristics. Int J Pharm. 2017;530(1-2):364–76.

    Article  CAS  Google Scholar 

  15. Santos JMRCA, Guthrie JT. Analysis of interactions in multicomponent polymeric systems: the key-role of inverse gas chromatography. Mat Sci Eng: R: Reports. 2005;50(3):79–107.

    Article  Google Scholar 

  16. Ho R, Heng JY. A review of inverse gas chromatography and its development as a tool to characterize anisotropic surface properties of pharmaceutical solids. KONA Powder Particle J. 2013;30:164–80.

    Article  CAS  Google Scholar 

  17. Mohammadi-Jam S, Waters KE. Inverse gas chromatography applications: a review. Adv Colloid Interf Sci. 2014;212:21–44. https://doi.org/10.1016/j.cis.2014.07.002.

    Article  CAS  Google Scholar 

  18. Voelkel A. Inverse gas chromatography: characterization of polymers, fibers, modified silicas, and surfactants. Crit Rev Anal Chem. 1991;22(5):411–39. https://doi.org/10.1080/10408349108051641.

    Article  CAS  Google Scholar 

  19. Sharif S, DiMemmo LM, Thommes M, Hubert M, Sarsfield BA. A simplified approach to determine effective surface area and porosity of low bulk density active pharmaceutical ingredients in early development. Adv Powder Technol. 2015;26(2):337–48.

    Article  CAS  Google Scholar 

  20. 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;142:216–21.

    Article  CAS  Google Scholar 

  21. Chakravarty P, Berendt RT, Munson EJ, Young VG Jr, Govindarajan R, Suryanarayanan R. Insights into the dehydration behavior of thiamine hydrochloride (vitamin B1) hydrates: part I. J Pharm Sci. 2010;99(2):816–27. https://doi.org/10.1002/jps.21876.

    Article  CAS  PubMed  Google Scholar 

  22. Chakravarty P, Berendt RT, Munson EJ, Young VG Jr, Govindarajan R, Suryanarayanan R. Insights into the dehydration behavior of thiamine hydrochloride (vitamin B1) hydrates: part II. J Pharm Sci. 2010;99(4):1882–95.

    Article  CAS  Google Scholar 

  23. Allan M, Chamberlain MC, Mauer LJ. RH-temperature stability diagram of the dihydrate, β-anhydrate, and α-anhydrate forms of crystalline trehalose. J Food Sci. 2019;84(6):1465–76. https://doi.org/10.1111/1750-3841.14591.

    Article  CAS  PubMed  Google Scholar 

  24. Nagase H, Endo T, Ueda H, Nakagaki M. An anhydrous polymorphic form of trehalose. Carbohydr Res. 2002;337(2):167–73. https://doi.org/10.1016/s0008-6215(01)00294-4.

    Article  CAS  PubMed  Google Scholar 

  25. Nagase H, Ogawa N, Endo T, Shiro M, Ueda H, Sakurai M. Crystal structure of an anhydrous form of trehalose: structure of water channels of trehalose polymorphism. J Phys Chem B. 2008;112(30):9105–11. https://doi.org/10.1021/jp800936z.

    Article  CAS  PubMed  Google Scholar 

  26. Rani M, Govindarajan R, Surana R, Suryanarayanan R. Structure in dehydrated trehalose dihydrate—evaluation of the concept of partial crystallinity. Pharm Res. 2006;23(10):2356–67.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank Dr. Anett Kondor, Dr. Daniel J. Burnett, and Mr. Armando Garcia from Surface Measurement Systems Ltd. for their insightful comments and advice. Dr. Apoorva Sarode from Genentech is thanked for help with statistical analysis.

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Funding

This work was funded by Genentech Inc.

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Authors and Affiliations

  1. Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, California, 94080, USA

    Minhthi Bui, Karthik Nagapudi & Paroma Chakravarty

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  1. Minhthi Bui
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  2. Karthik Nagapudi
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  3. Paroma Chakravarty
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Contributions

Minhthi Bui: analysis, investigation, validation, and writing

Karthik Nagapudi: conceptualization, supervision, review, and editing

Paroma Chakravarty: conceptualization, analysis, supervision, review, and editing

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Correspondence to Paroma Chakravarty.

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Bui, M., Nagapudi, K. & Chakravarty, P. Determination of BET Specific Surface Area of Hydrate-Anhydrate Systems Susceptible to Phase Transformation Using Inverse Gas Chromatography. AAPS PharmSciTech 23, 237 (2022). https://doi.org/10.1208/s12249-022-02395-6

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