Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, H-6720 Szeged, Eötvös u. 6, Hungary.
Laboratory of Transfer Phenomena, Faculty of Mechanical Engineering and Process Engineering, University of Sciences and Technology Houari Boumediene, BP32 Bab Ezzouar, 16111 Algiers, Algeria.
Eur J Pharm Sci. 2019 Jan 15;127:351-362. doi: 10.1016/j.ejps.2018.09.003. Epub 2018 Sep 6.
The in-line control of pharmaceutical processes has become a necessary tool for the evaluation and follow-up of pharmaceutical dosage forms. In this study, a novel approach to the evaluation of conditions established in a conical fluid bed granulator during the in-situ and spray-on fluid bed melt granulation (FBMG) techniques was developed. The determination of temperature mappings allowed the characterization of the critical zones during the melt granulation and the prediction of the volume of the wetting zone, hence enabling the identification of the areas of optimal granule growth. Two grades of polyethylene glycol (PEG 2000 and 6000) were used as meltable binders in three binder spraying rates and droplet size fractions for spray-on and three binder particle sizes and contents for in-situ. The results showed the presence of intense heat exchange in the bottom of the bed during the in-situ technique and under the spraying nozzle during the spray-on technique, identified as the wetting zone. Isotherm maps enabled the identification of the transition between the wetting, cooling and consolidation zones for the spray-on and the cooling zone for the in-situ technique. The shape and volume of the wetting zone was highly dependent on binder spraying rate and spraying pressure for spray-on and binder particle size and content for in-situ FBMG. Granule size and size distribution were correlated to the volume of the wetting zone and an optimized wetting volume interval was determined for both spray-on and in-situ techniques for the optimal quality attributes of the granules.
在线控制制药工艺已成为评估和跟踪药物剂型的必要工具。在这项研究中，开发了一种新颖的方法来评估锥形流化床造粒机中建立的条件，用于原位和喷雾流化床熔融造粒（FBMG）技术。温度测绘的确定允许对熔融造粒过程中的关键区域进行表征，并预测润湿区域的体积，从而能够识别最佳颗粒生长区域。两种等级的聚乙二醇（PEG 2000 和 6000）被用作可熔融的粘合剂，在三种粘合剂喷雾速率和液滴尺寸分数下进行喷雾，以及三种粘合剂粒径和含量下进行原位。结果表明，在原位技术中床层底部和喷雾技术下的喷雾喷嘴处存在强烈的热交换，这被认为是润湿区域。等温线图能够识别喷雾的润湿、冷却和固结区之间的过渡区，以及原位技术的冷却区。喷雾的润湿区域的形状和体积高度依赖于粘合剂喷雾速率和喷雾压力，而原位 FBMG 的则依赖于粘合剂粒径和含量。颗粒大小和分布与润湿区域的体积相关，对于喷雾和原位技术，确定了优化的润湿体积间隔，以获得颗粒的最佳质量属性。
