title: A logical stepwise approach to laser diffraction particle size distribution analysis methods development and validation.
abstract: In this study, a logical, stepwise, efficient approach was used to develop and validate particle size distribution analysis methods for 58 different pharmaceutical bulk powders in a timely fashion. Image analysis was used to determine particle morphology and laser diffraction particle size distribution analysis was used to evaluate the dispersion medium, dispersion concentration, sonication time, and dispersion stability. Ruggedness validation was performed, by two different analysis, on different days, with different instruments on two preparations each of two different lots of material. It was determined that if the relative standard deviation (RSD) of the median volume diameters (d50) of the four preparations for each lot was below 20%, the method was suitably rugged for use in a quality control setting. Data for methyldopa, metoprolol tartrate, and metronidazole are presented as typical method validation results for three different modes of analysis. Data at three points (d10, d50, and d90) on the distributions were tabulated and evaluated for all 58 methods validated. The median volume diameter (d50) was found to be adequate for method validation. The approach rapidly generated valid, reproducible particle size distribution analysis methodology.
authors.affiliation: Geneva Pharmaceuticals, Inc., a Novartis Company, Broomfield, Colorado 80038-0446, USA.
authors.forename: D
authors.initials: D
authors.lastname: Barber
authors.forename: J
authors.initials: J
authors.lastname: Keuter
authors.forename: K
authors.initials: K
authors.lastname: Kravig
mesh_terms: D002626:Chemistry, Pharmaceutical; D007091:Image Processing, Computer-Assisted; D007834:Lasers; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis; D011208:Powders; D015203:Reproducibility of Results
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders