Image Analysis of the Shape of Granulated Powder Grains SERGIO ALMEIDA-PRIETO, JOSE ´ BLANCO-ME ´ NDEZ, FRANCISCO J. OTERO-ESPINAR Departamento de Farmacia y Tecnologı ´a Farmace ´utica, Facultade de Farmacia, Universidade de Santiago de Compostela, Campus Universitario sur s/n. 15076 Santiago de Compostela, A Corun ˜a, Spain Received 4 February 2003; revised 28 May 2003; accepted 10 September 2003 ABSTRACT: This study presents and evaluates two new form factors for the charac- terization of pharmaceutical microparticles using image analysis techniques. The first factor, denoted Vr, is mean percentage variation in radial chord length (for a large number of radial chords drawn at small angular intervals) with respect to mean radial chord length. The second factor, denoted Vp, is percentage deviation of measured perimeter from the perimeter of a circle with radius equal to the mean radial chord length of the particle. Considering both ideal shapes and real pharmaceutical particle popula- tions, these factors are compared with other form factors widely used in pharmaceutical technology. Our results indicate that Vr and Vp allow effective assessment of whether the particles of a given population show pharmaceutically significant deviations from sphericity. The two factors additionally facilitate identification of the basic shapes of particle outlines (notably ellipsoid, rectangular, and irregular). These factors may thus be of value for the characterization and monitoring of pharmaceutical pelleting processes. ß 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:621– 634, 2004 Keywords: image analysis; physical characterization; morphology; extrusion; spher- onization; powder technology; granulation; microencapsulation; shape analysis; pellets INTRODUCTION In the morphological characterization of a particle by image analysis (IA), three basic questions are of interest. 1,2 First, what is the basic geometric shape of the outline of the particle? Second, what degree of roundedness does the particle show: are its vertices sharp or blunt? Third, what is the surface texture? The most frequent approach is to consider a given particle as corresponding to an ideal shape and to characterize the particle in terms of devia- tion from that shape. In the context of pharma- ceutical technology, and more specifically that of granulation and pelleting, the typical approach is to consider particles as basically spherical, and to characterize them in terms of deviation from the ideal sphere. However, a review of the literature indicates that numerous different form factors have been proposed for the evaluation of spheri- city: these parameters are defined in diverse ways and are based on diverse measurement procedures. These different form factors include the Heywood factor or factors, 3 which classify particle shape into different categories. In addition, Chap- man et al. 4 proposed characterization of pellet sphericity on the basis of one-plane critical stability, and this approach has been adopted in some subsequent studies. 5,6 Other authors 7 have proposed joint evaluation of several parameters for evaluation of sphericity and elongation; namely, roughness, pellips, rectang, modelx, elongation, circularity, and roundness. Again, however, these latter terms (elongation, circularity, and roundness) are widely used with disparate meanings. Thus, the parameter 4p  area/perimeter 2 proposed by Cox 8 is denoted ‘‘circularity’’ by some authors, 7 whereas other JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 93, NO. 3, MARCH 2004 621 Correspondence to: Francisco J. Otero-Espinar (Telephone: 34 981 563100, ext. 14878; Fax: 34 981 547148; E-mail: ffrotero@usc.es) Journal of Pharmaceutical Sciences, Vol. 93, 621–634 (2004) ß 2004 Wiley-Liss, Inc. and the American Pharmacists Association