Purpose

MALCORE^®, a manufacturing technology of drug-containing particles (DCPs) for coating, consists of a 2-step melt granulation process. The drug-layering process in the technology is important for determining the characteristics of the resulting DCPs. However, the effect of the manufacturing conditions of the drug-layering process on particle characteristics has not been clarified. The aim of this study was to investigate the effect of the manufacturing conditions for MALCORE^® on particle characteristics using the design of experiments (DoE) method.

Method

A high-shear granulator was used in the drug-layering process, and the product temperature, melt granulation time, and blade rotation speed were selected as input factors for the DoE. The available yield, d₁₀ and d₅₀, flowability, particle strength, and drug dissolution of DCPs were evaluated, and the relationship between the manufacturing conditions and particle characteristics was clarified using statistical methods.

Results

The available yield and d₅₀ were affected by all manufacturing conditions while the particle strength was affected only by the blade rotation speed. Drug dissolution was unaffected by the manufacturing conditions. The predicted and measured values in the design space of the manufacturing conditions constructed based on these results were almost identical, thereby indicating the validity of the DoE.

Conclusion

The results of this study revealed the effect of manufacturing conditions on particle characteristics for a unique manufacturing technology MALCORE^®, in which the drug is layered on the core particles by melt granulation. The findings provide useful information for the implementation of MALCORE^® in pharmaceutical formulation development.

中文翻译：

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使用实验设计研究制造条件对新型熔融造粒技术 MALCORE® 药物分层过程中颗粒特性的影响

目的

MALCORE ^®是一种用于包衣的含药颗粒（DCP）的制造技术，由两步熔融造粒工艺组成。该技术中的药物分层过程对于确定所得 DCP 的特性非常重要。然而，药物层积工艺的制造条件对颗粒特性的影响尚未明确。本研究的目的是利用实验设计 (DoE) 方法研究 MALCORE ^®的制造条件对颗粒特性的影响。

方法

药物分层过程中使用高剪切造粒机，选择产品温度、熔融造粒时间和刀片旋转速度作为 DoE 的输入因素。评估了DCP的有效产率、d ₁₀和d _{50 、流动性、颗粒强度和药物溶出度，并使用统计方法阐明了制造条件和颗粒特性之间的关系。}

结果

可用产量和d ₅₀受到所有制造条件的影响，而颗粒强度仅受叶片旋转速度的影响。药物溶出度不受生产条件的影响。基于这些结果构建的制造条件的设计空间中的预测值和测量值几乎相同，从而表明DoE的有效性。

结论

这项研究的结果揭示了制造条件对独特制造技术 MALCORE ^®颗粒特性的影响，其中药物通过熔融造粒分层在核心颗粒上。研究结果为在药物制剂开发中实施MALCORE ^®提供了有用的信息。