From Micromeritics to Nanomeritics: A Review and Integrative Framework for Bridging the Physicochemical-Biological Continuum

Few nanoparticle-enabled medicinal products (NEPs) are commercially available today, despite the introduction of Doxil, the first Food and Drug Administration (FDA)-approved nanotechnology drug product, in 1995. One hurdle in developing NEPs is the need for specialized tools to characterize and detect nanoscale materials under various conditions (e.g., during manufacturing or after administration into the body). Another significant scientific challenge lies in characterizing NEPs. For example, interpreting particle-sizing results is difficult because many conventional detection methods do not allow scientists to analyze or confirm the size and properties of NEPs. While characterization methods for larger particles (1 µm to 1 mm) are well established, the same cannot be said for nanoscale particles. In fact, the physical and biopharmaceutical properties of particles made from the same material but differing in size can vary significantly, particularly for particles measuring approximately 1 nm to 100 nm. These challenges have led to a re-evaluation of the characterization and interpretation tools essential for developing NEPs. In this review, pharmaceutical micromeritics is first summarized, including the characterization techniques for particles in the 1 µm to 1 mm size range. Then, the concept of nanomeritics is discussed. Nanomeritics differs from micromeritics by focusing on the characterization of nanoscale particles and extends the field to its implications in biological environments. Nanomeritics is introduced by (1) defining the nanoparticle size range, (2) providing a comprehensive overview of the methods to characterize nanoparticles, (3) proposing orthogonal characterization guidelines, and (4) identifying how NEPs interact in biological environments. In this review, the methodologies and limitations of particle sizing and characterization methods are also discussed.