Purpose

Particle size control is of vital importance to the performance and manufacturability of a solid drug substance used in an oral dosage pharmaceutical product. Numerous options for control are available to engineers and scientists engaged in process design; this study seeks to demonstrate the steps taken to define the optimal solution.

Method

Wet milling, terminal size control though crystallisation alone and dry milling were studied as potential methods of particle size control. Laboratory experiments were conducted for each of these options. Long-term manufacturing cost implications were estimated, while a qualitative analysis of factors such as regulatory burden was conducted.

Results

Each control option was shown to produce an active pharmaceutical ingredient (API) of sufficient quality via a robust and scalable process. Differences emerged when each method was subjected to a broader analysis of supporting factors (regulatory, cost, supply chain).

Conclusion

In this case, wet milling was selected as the most cost-effective option for control with the lowest expected regulatory burden. Regardless of the method chosen for this particular case, the framework should have broad applicability to different APIs.

中文翻译：

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活性药物成分粒径控制的技术和经济影响分析

目的

粒度控制对于口服药物产品中使用的固体药物的性能和可制造性至关重要。从事过程设计的工程师和科学家可以使用许多控制选项。本研究旨在证明定义最佳解决方案所采取的步骤。

方法

研究了湿磨，仅通过结晶控制最终粒度和干磨作为控制粒度的潜在方法。针对这些选项中的每一个进行了实验室实验。估计了对长期制造成本的影响，同时对诸如监管负担之类的因素进行了定性分析。

结果

通过健壮且可扩展的流程，每个对照选项均显示出可产生足够质量的活性药物成分（API）。当对每种方法进行支持因素（监管，成本，供应链）的更广泛分析时，就会出现差异。

结论

在这种情况下，湿磨被选为控制成本最低，预期监管负担最低的选项。无论为这种特定情况选择哪种方法，该框架都应该对不同的API具有广泛的适用性。