2.3. Characterization of the Pellets

Pellet size and shape was determined using an image processing and analysis system comprised of a stereomicroscope, top cold light source (Olympus SZX9, Tokyo, Japan and Highlight 3100, Olympus Optical), video camera (VC-2512, Sanyo Electric, Osaka, Japan), and software (Quantimet 500, Cambridge, UK). About 100 pellets were examined at a total magnification of ×32.5. Mean pellet diameter was expressed as equivalent circle diameter (diameter of a circle with the same area as the projected pellet) and particle shape as aspect ratio (quotient of longest and shortest orthogonal dimension). Moisture content (% weight change on dry basis) of the pellets was determined using a moisture analyzer (Unibloc MOC63u; Shimadzu Corporation, Kyoto, Japan) (accuracy ±0.001 g) by exposing approximately 5 g samples at 105 °C for 30 min.

For the determination of pellet density, helium pycnometry was applied (Ultrapycnometer 1000, Quantachrome Instruments, Boynton Beach, Florida, FL, USA). The instrument was calibrated using a standard 7.0699 cm³ steel ball. Samples were accurately weighed (3 decimals) and purged for 10 min before measurement. Sample volume (average of 10 runs) was measured from the displaced gas. Measurements were made in triplicate and mean values and standard deviations were calculated. According to the USP 31, Chapter <699>, pycnometric density is a convenient measurement of the density of pharmaceutical powders. This differs from the granular density, where impenetrable voids or inaccessible pores may alter the measurement. In the case of pellets made by extrusion/spheronization, closed pores may form during hot air drying due to the operation of capillary forces, resulting in larger measured volume or lower density [13]. For this reason, the term “apparent” pellet density is adopted in this work.

Photomicrographs were taken with a scanning electron microscope (SEM) (JEOL JSM-6390LV, Tokyo, Japan) and the morphology of plain and coated pellets was examined. Photomicrographs of the cross sections of the pellets were also taken in backscattered electron mode in order to demonstrate the coating surface layer. Unfortunately, since the emission of backscattered electrons and/or brightness depends on the atomic number of the chemical elements in the pellet, the identification of the coating layer was only possible for pellets containing barium sulfate with a high atomic number.