Department of Pharmaceutical Technology, Medical University of Gdansk, Gdansk, Poland.
Department of Pharmaceutical Technology, Student Chapter of ISPE, Gdansk, Poland.
Drug Dev Ind Pharm. 2020 Apr;46(4):547-556. doi: 10.1080/03639045.2020.1734020. Epub 2020 Mar 4.
The purpose of this study was to apply the rheological measurements to assess the flow properties of powders and granules and to compare the results with the standard pharmacopeial tests. Quality by design approach was utilized to better understand the compression of the solids into minitablets. Insights are provided regarding the methodology of rheological properties of powders and granules using powder flow analyzer (PFA). The 'six sigma' approach was presented as a tool for assessment of the minitablets manufacturing process. Pharmacopeial methods and rheological tests using PFA were performed to assess the flow properties of designed powder and fractionated granule mixtures - placebo and with benzodiazepines. Compression of 2.5 and 3 mm minitablets was carried out and the compression force registered during the process and weight uniformity were statistically analyzed by calculating the capability indices. The flow rate measurement and cohesion test (PFA test) resulted in the best differentiation between mixtures. Higher values of capability indices were obtained for processes in which granule mixtures with better flow properties were compressed and 3 mm minitablets were produced and the usefulness of QbD tools in assessment of minitablets compression process was confirmed. Performed study showed that the flow properties are the critical quality attributes determining the performance of minitablets compression. The cohesion test is the most discriminative to distinguish the analyzed mixtures. Capability indices can be used to assess the manufacturing process as a useful tool in pharmaceutical development of minitablets.
本研究旨在应用流变测量来评估粉末和颗粒的流动特性，并将结果与标准药典测试进行比较。采用质量源于设计方法来更好地理解固体压缩成迷你片剂的过程。提供了关于使用粉末流分析仪（PFA）评估粉末和颗粒流变特性的方法学的见解。提出了“六西格玛”方法作为评估迷你片剂制造过程的工具。进行了药典方法和使用 PFA 的流变测试，以评估设计的粉末和分级颗粒混合物（安慰剂和苯并二氮䓬类药物）的流动特性。对 2.5 和 3 毫米迷你片剂进行了压缩，并通过计算能力指数对压缩过程中记录的压缩力和重量均匀性进行了统计分析。流速测量和内聚性测试（PFA 测试）导致混合物之间的最佳区分。在压缩具有更好流动特性的颗粒混合物并生产 3 毫米迷你片剂的过程中，获得了更高的能力指数值，证实了 QbD 工具在评估迷你片剂压缩过程中的有用性。进行的研究表明，流动特性是决定迷你片剂压缩性能的关键质量属性。内聚性测试是区分分析混合物的最具辨别力的测试。能力指数可用于评估制造过程，作为迷你片剂药物开发的有用工具。
