Langner Marcel, Priese Florian, Wolf Bertram
IDT Biologika, Am Pharmapark, 06861 Dessau-Roßlau, Germany.
Department of Applied Biosciences and Process Engineering, Anhalt University of Applied Sciences, Bernburger Straße 55, 06366 Köthen, Germany.
Pharmaceutics. 2024 Oct 8;16(10):1307. doi: 10.3390/pharmaceutics16101307.
BACKGROUND/OBJECTIVES: Coated drug pellets enjoy widespread use in hard gelatine capsules. In heterogeneous pellets, the drug substance is layered onto core pellets. Coatings are often applied to generate a retarded release or an enteric coating.
In the present study, the thickness of a polymer coating layer on drug pellets was correlated to the drug release kinetics.
The question should be answered whether it is possible to stop the coating process when a layer thickness referring to an intended drug release is achieved. Inert pellets were first coated with sodium benzoate and second with different amounts of water insoluble polyacrylate in a fluidized bed apparatus equipped with a Wurster inlet. The whole process was controlled in-line and at-line with process analytical technology by the measurement of the particle size and the layer thickness. The in-vitro sodium benzoate release was investigated, and the data were linearized by different standard models and compared with the polyacrylate layer thickness. With increasing polyacrylate layer thickness the release rate diminishes. The superposition of several processes influencing the release results in release profiles corresponding approximately to first order kinetics. The coating layer thickness corresponds to a determined drug release profile.
The manufacturing of coated drug pellets with intended drug release is possible by coating process control and layer thickness measurement. Preliminary investigations are necessary for different formulations.
背景/目的：包衣药物微丸在硬明胶胶囊中广泛应用。在非均一微丸中，药物层叠在微丸芯上。包衣常用于实现缓释或肠溶包衣。
在本研究中，药物微丸上聚合物包衣层的厚度与药物释放动力学相关。
当达到与预期药物释放相关的层厚时，是否有可能停止包衣过程这一问题应得到解答。惰性微丸首先用苯甲酸钠包衣，然后在配备Wurster入口的流化床装置中用不同量的水不溶性聚丙烯酸酯包衣。通过测量粒径和层厚，采用过程分析技术对整个过程进行在线和离线控制。研究了苯甲酸钠的体外释放情况，并通过不同的标准模型对数据进行线性化处理，并与聚丙烯酸酯层厚进行比较。随着聚丙烯酸酯层厚的增加，释放速率降低。影响释放的多个过程的叠加导致释放曲线大致符合一级动力学。包衣层厚度对应于确定的药物释放曲线。
通过包衣过程控制和层厚测量，可以制造出具有预期药物释放的包衣药物微丸。对于不同的制剂，需要进行初步研究。
