Near-Infrared Spectroscopy and Imaging for the Monitoring of Powder Blend Homogeneity ARWA S. EL-HAGRASY, 1 HANNAH R. MORRIS, 2 FRANK D'AMICO, 3 ROBERT A. LODDER, 4 JAMES K. DRENNEN III 1 1 Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, Pennsylvania 15282 2 Carnegie Mellon Research Institute, Pittsburgh, Pennsylvania 3 Department of Computational Mathematics, McAnulty College and Graduate School of Liberal Arts, Duquesne University, Pittsburgh, Pennsylvania 4 College of Pharmacy, University of Kentucky, Lexington, Kentucky Received 15 November 2000; revised 27 March 2001; accepted 28 March 2001 ABSTRACT: In-process testing requirements for adequacy of mixing are established in 21 CFR 211.110(a)(3). Considering also, the U.S. Food and Drug Administration's draft guidance published in 1999 (Guidance for Industry, ANDAs: Blend Uniformity Analysis; http://www.fda.gov/cder/guidance/index.htm), the importance of when and how to perform blend uniformity analysis is obvious. Near-infrared (NIR) spectroscopy was used noninvasively, in this study, to monitor powder blend homogeneity. Powder mixtures consisting of salicylic acid and Fast-Flo lactose were blended in an 8-qt. V-Blender. Optical ports installed at six positions on the blender allowed spectral collection using ®ber optics. A traditional thief probe was used to collect powder samples for ultraviolet (UV) reference analysis. The blender was stopped at preselected time points for collection of NIR and UV data. Several algorithms and sampling protocols were studied to identify an optimum methodology for blend homogeneity determination. The blending process was also monitored with an InSb imaging camera for comparison with the traditional NIR spectroscopy and UV reference data. Data analysis indicates that multiple sampling points were essential for accurate and precise estimation of mixing end points. Moreover, multiple runs of identical blends often display homogeneity at unique end points, thus demonstrating the potential advantage of monitoring every blend. ß 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1298±1307, 2001 Keywords: NIR (near-infrared); blend uniformity analysis; homogeneity; process control; imaging INTRODUCTION In light of the ongoing discussion about the U.S. Food and Drug Administration's (FDA's) draft guidance on blend uniformity analysis (Guidance for Industry, ANDAs: Blend Uniformity Analysis; http://www.fda.gov/cder/guidance/index.htm) and the general lack of understanding of blending processes, new technology allowing improved control of such mixing processes should be of signi®cant interest to a large audience. Blending of solids and semisolids is a critical step in the production of many pharmaceutical products. Homogeneity of blends is essential for obtaining high quality products of uniform content. The intent of any blending process is to achieve a uni- form mixture of all ingredients including active and excipient(s). Lack of content uniformity can JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 90, NO. 9, SEPTEMBER 2001 1298 Correspondence to: J. K. Drennen, III (Telephone: 412-396- 6315; Fax: 412-396-4660; E-mail: drennen@duq.edu) Journal of Pharmaceutical Sciences, Vol. 90, 1298±1307 (2001) ß 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association