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Detailed Morphological Characterization of Nanocrystalline Active Ingredients in Solid Oral Dosage Forms Using Atomic Force Microscopy

Abstract

The characterization of nanocrystalline active ingredients in multicomponent formulations for the design and manufacture of products with increased bioavailability is often challenging. The purpose of this study is to develop an atomic force microscopy (AFM) imaging method for the detailed morphological characterization of nanocrystalline active ingredients in multicomponent oral formulations. The AFM images of aprepitant and sirolimus nanoparticles in aqueous suspension show that their sizes are comparable with those measured using dynamic light scattering (DLS) analysis. The method also provides information on a wide-sized range of particles, including small particles that can often only be detected by DLS when larger particles are removed by additional filtration steps. An expected advantage of the AFM method is the ability to obtain a detailed information on particle morphology and stiffness, which allows the active pharmaceutical ingredient and excipient (titanium dioxide) particles to be distinguished. Selective imaging of particles can also be achieved by varying the surface properties of the AFM solid substrate, which allows to control the interactions between the substrate and the active pharmaceutical ingredient and excipient particles. AFM analysis in combination with other methods (e.g., DLS), should facilitate the rational development of formulations based on nanoparticles.

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Acknowledgments

The authors thank M. Kozaki (Kowa Company Ltd., Japan) for supplying samples of titanium dioxide and for fruitful discussions regarding the use of nanosized excipients in solid oral dosage forms.

Funding

This work was supported in part by the Research on Regulatory Harmonization and Evaluation of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics project of the Japanese Agency for Medical Research and Development (17mk0101038j0303).

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Correspondence to Kumiko Sakai-Kato.

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Sakai-Kato, K., Nanjo, K., Takechi-Haraya, Y. et al. Detailed Morphological Characterization of Nanocrystalline Active Ingredients in Solid Oral Dosage Forms Using Atomic Force Microscopy. AAPS PharmSciTech 20, 70 (2019). https://doi.org/10.1208/s12249-018-1259-x

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  • DOI: https://doi.org/10.1208/s12249-018-1259-x

KEY WORDS

  • nanocrystalline active ingredient
  • excipient
  • atomic force microscopy
  • dynamic light scattering