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

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• 作者：Marija Djoki膰^a ; Jelena Djuri&scaron ; ^a ; Ljiljana Solomun^a ; Kyriakos Kachrimanis^b ; Zorica Djuri膰^a ; Svetlana Ibri膰^a ; ^{svetlana.ibric@pharmacy.bg.ac.rs" class="auth_mail} ; ^{ibric@beotel.net" class="auth_mail}
• 关键词：Jet-milling ; Carbamazepine ; Factorial screening design ; Particle size ; Polymorphism ; Quality by design
• 刊名：Chemical Engineering Research and Design
• 出版年：March, 2014
• 年：2014
• 卷：92
• 期：3
• 页码：500-508
• 全文大小：3296 K

文摘

The purpose of this study was to investigate the influence of spiral jet-milling process on the physicochemical characteristics of 伪 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 5 渭m, as well as, in initial polymorph form existence after jet-milling through combination and interaction of input variables.