The influence of spiral jet-milling on the physicochemical properties of carbamazepine form III crystals: Quality by design approach

• Published in: Chemical engineering research & design 2014-03, Vol.92 (3), p.500-508
• Main Authors: Djokić, Marija, Djuriš, Jelena, Solomun, Ljiljana, Kachrimanis, Kyriakos, Djurić, Zorica, Ibrić, Svetlana
• Format: Article
• Language: English
• Subjects: Carbamazepine; Design engineering; Differential scanning calorimetry; Drugs; Factorial screening design; Jet-milling; Mathematical models; Nozzles; Particle size; Particle size distribution; Pharmaceuticals; Polymorphism; Quality by design; Spirals
• ISSN: 0263-8762; 1744-3563
• DOI: 10.1016/j.cherd.2013.09.011

•Design space of jet milling process for model drug was established.•Jet milling used for micronizing of drug preserved its crystal structure.•Critical process parameters for jet milling were identified. The purpose of this study was to investigate the influence of spiral jet-milling process on the physicochemical characteristics of α polymorphic active pharmaceutical ingredient, using Carbamazepine form III as a model drug, and taking into consideration Quality by Design (QbD) approach to pharmaceutical development. A 2(4-1) factorial screening design was implemented to identify the spiral jet-milling process variables that significantly affect the particle size distribution of milled samples. Diameter of injector nozzles, diameter of ring nozzles and air pressure were selected for further analysis using a 2(3-1) factorial experimental design. Particle size distribution of additional samples was determined, while physicochemical properties were examined by differential scanning calorimetry (DSC), hot-stage polarized microscopy (HSPM), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and compared to those of un-milled drug. The gathered results shown that applied experimental design approach is capable to predict material behavior and could help in better understanding of material behavior during jet-milling process. Created design space (DS) provides assurance of product quality, expressed as the powder particle sizes lower than 5μm, as well as, in initial polymorph form existence after jet-milling through combination and interaction of input variables.