Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore, 117576, Singapore.
Critical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT Alliance for Research and Technology, Singapore, 138602, Singapore.
Pharm Res. 2022 Feb;39(2):411-421. doi: 10.1007/s11095-021-03155-0. Epub 2022 Feb 4.
Industrial implementation of continuous oral solid dosage form manufacturing has been impeded by the poor powder flow properties of many active pharmaceutical ingredients (APIs). Microfluidic droplet-based particle synthesis is an emerging particle engineering technique that enables the production of neat or composite microparticles with precise control over key attributes that affect powder flowability, such as particle size distribution, particle morphology, composition, and the API's polymorphic form. However, the powder properties of these microparticles have not been well-studied due to the limited mass throughputs of available platforms. In this work, we produce spherical API and API-composite microparticles at high mass throughputs, enabling characterization and comparison of the bulk powder flow properties of these materials and greater understanding of how particle-scale attributes correlate with powder rheology.
A multi-channel emulsification device and an extractive droplet-based method are harnessed to synthesize spherical API and API-excipient particles of artemether. As-received API and API crystallized in the absence of droplet confinement are used as control cases. Particle attributes are characterized for each material and correlated with a comprehensive series of powder rheology tests.
The droplet-based processed artemether particles are observed to be more flowable, less cohesive, and less compressible than conventionally synthesized artemether powder. Co-processing the API with polycaprolactone to produce composite microparticles reduces the friction of the powder on stainless steel, a common equipment material.
Droplet-based extractive solidification is an attractive particle engineering technique for improving powder processing and may aid in the implementation of continuous solid dosage form manufacturing.
由于许多活性药物成分 (API) 的粉末流动性能较差，连续口服固体制剂制造的工业化实施受到了阻碍。微流控液滴基粒子合成是一种新兴的粒子工程技术，可生产具有精确控制关键属性的纯或复合微粒子，这些属性会影响粉末流动性，例如粒径分布、颗粒形态、成分和 API 的多晶型形式。然而，由于可用平台的质量通量有限，这些微粒子的粉末性质尚未得到很好的研究。在这项工作中，我们以高质量通量生产球形 API 和 API-复合微粒子，从而能够对这些材料的体粉末流动性能进行表征和比较，并更好地了解颗粒尺度属性与粉末流变性的相关性。
利用多通道乳化装置和提取液滴法合成青蒿素 API 和 API-赋形剂微球。将收到的 API 和在没有液滴限制的情况下结晶的 API 用作对照品。对每种材料的颗粒特性进行了表征，并与一系列全面的粉末流变性测试相关联。
与常规合成的青蒿素粉末相比，基于液滴的加工青蒿素颗粒表现出更好的流动性、更小的粘性和更小的可压缩性。将 API 与聚己内酯共加工以生产复合微粒子可降低粉末对不锈钢的摩擦，不锈钢是一种常见的设备材料。
基于液滴的萃取固化是一种有吸引力的粒子工程技术，可改善粉末加工性能，并可能有助于连续固体制剂制造的实施。
