Oral Drug Product Development, Hovione FarmaCiencia SA, Estrada do Paço do Lumiar, Campus do Lumiar, Edifício S, 1649-038, Lisbon, Portugal.
Merlin Powder Characterisation Ltd, Unit D1, The Wallows Industrial Estate, Fens Pool Avenue , Brierley Hill, DY5 1QA, West Midlands, UK.
AAPS PharmSciTech. 2022 Mar 21;23(4):96. doi: 10.1208/s12249-022-02248-2.
Amorphous solid dispersions (ASDs) are a proven method of improving the solubility and bioavailability of poorly soluble compounds. Immediate release tablets are frequently used as final dosage form for ASDs. Increasing tableting process throughput during clinical development requires using larger, faster tablet presses which subject materials to higher strain rate. Many pharmaceutical materials show strain rate sensitivity, i.e., yield pressure sensitivity to compression speed. Currently, there is only scattered information available in scientific literature on how ASDs behave under different tablet compression speeds. The purpose of this study was to examine spray-dried ASDs' sensitivity to strain rate under compression in a comprehensive study. We also investigated the drivers for such a strain sensitive behavior. A set of sample spray-dried powders, selected for their range of properties, were compressed using a simulated Korsch XL100 profile at 3 and 30 RPM and V-profile at 0.1 and 300 mm/s on a Phoenix compaction simulator. The sample set included samples with varying API content (0-50% w/w), stabilizing polymer (HPMC, HPMC-AS, PVP-VA), particle size, and bulk densities, produced on spray driers from lab to commercial scale. We identified that all ASD samples showed plastic flow and deformation behavior and form robust compacts at slow compression speeds. At high speed, tablet defects occurred. The strain rate sensitivity observed in this study was comparable or slightly superior to that observed for microcrystalline cellulose, known to be a mildly strain rate-sensitive material. We showed that compression speed is a critical process parameter for ASD-containing tablets.
无定形固体分散体（ASD）是一种已被证实的提高难溶性化合物溶解度和生物利用度的方法。速释片剂通常被用作 ASD 的最终剂型。在临床开发过程中，提高压片过程的产量需要使用更大、更快的压片机，这会使材料承受更高的应变速率。许多药物材料表现出应变率敏感性，即屈服压力对压缩速度敏感。目前，科学文献中仅有关于 ASD 在不同片剂压缩速度下的行为的零散信息。本研究的目的是全面研究喷雾干燥 ASD 在压缩过程中对应变速率的敏感性。我们还研究了这种应变敏感行为的驱动力。一组具有不同性质的喷雾干燥粉末样品，根据其性质范围进行选择，使用模拟 Korsch XL100 曲线在 3 和 30 RPM 以及 V 曲线在 0.1 和 300mm/s 下在 Phoenix 压片机模拟器上进行压缩。样品集包括 API 含量（0-50%w/w）、稳定剂聚合物（HPMC、HPMC-AS、PVP-VA）、粒径和堆密度不同的样品，由实验室到商业规模的喷雾干燥器生产。我们发现所有 ASD 样品均表现出塑性流动和变形行为，并在低速压缩速度下形成坚固的片剂。在高速下，片剂出现缺陷。在本研究中观察到的应变速率敏感性与微晶纤维素相当或略优，后者被认为是一种轻度应变速率敏感材料。我们表明，压缩速度是含 ASD 片剂的关键工艺参数。
