Developments in Scanning Electron Microscopy for Tablet and Granule Characterization
Recent advances in SEM, particularly the incorporation of automation and software, have made simpler, lower-end SEM instruments easy to operate and have improved the capabilities of larger, sophisticated instruments.
Scanning electron microscopy (SEM) provides a qualitative assessment of size, shape, morphology, porosity, size distribution,
crystal form, and consistency of powders or compressed dosage forms (see Figure 1). This information can be correlated to
assess dissolution behavior, bioavailability, and crystalline structure. SEM images also help analysts determine whether particles
are maintaining desired physical characteristics during processing, including after compaction or direct compression (see
Figures 2, 3).
Figure 1: (FIGURE COURTESY OF FEI COMPANY)
As an analytical tool, electron microscopy in general has changed extensively, especially with the incorporation of automation
and software. An SEM instrument in the 1940s, for example, had a resolving power of about 50 nm and a magnification of 8000×.
Today, SEM devices have resolving power of 1 nm and a magnification as high as 400,000× (1). Simple, low-end SEM instruments
now have touchscreen user interfaces and provide a fast visual inspection of samples. On the very high end, transmission
electron microscopes have recently demonstrated the capability to identify individual atoms (2).
"Commonly called the laboratory 'workhorse,' microscopes have come a long way to the present day in terms of advancements
in automation, higher precision, and better resolution," says Sharon Mathews, a research associate for Technical Insights
at Frost & Sullivan. "With digital imaging gaining momentum in the recent years, microscope manufactures are now designing microscopes with image
analysis at the forefront" (see sidebar, "Microscopy advances").
Figure 2: (FIGURE COURTESY OF FEI COMPANY)
Mathews attributes the following factors as primary drivers to increasing use of microscopy:
Innovations in digital imaging: "Digital imaging offers numerous capabilities to the microscopy market opportunities in terms
of enhanced features to extract information or modify the images captured. The convergence of digital imaging and information
technology is enabling microscope manufacturers in tailoring their product offerings to suit the specific requirements."
Cost effectiveness and ease of operation: "With the diversity of the end-user and lower cost, the microscopy market is steadily
growing. Simple automated systems are now increasing the usage of microscopes."
Novel applications: "The clinical market, namely, pathology, cytology, and hematology have greatly relied on microscopy over
the years. Owing to new imaging applications and research funding, the pharmaceutical, academic, and government laboratories
are now propelling the microscopy market. Live cell imaging, molecular imaging enabling identification of events at molecular
level and specific applications such as dynamic behavior of cells ... has been responsible for the rapid progress of the microscopy