Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, California, 94080, USA.
AAPS PharmSciTech. 2021 Dec 20;23(1):28. doi: 10.1208/s12249-021-02160-1.
Spray-drying dispersion (SDD) is a well-established manufacturing technique used to prepare amorphous solid dispersions (ASDs), allowing for poorly soluble drugs to have improved bioavailability. However, the process of spray-drying with multiple factors and numerous variables can lead to a lengthy development timeline with intense resource requirements, which becomes the main obstacle limiting spray-drying development at the preclinical stage. The purpose of this work was to identify optimized preset parameters for spray-drying to support the early development of ASDs suitable for most circumstances rather than individual optimization. First, a mini-DoE (Design of Experiment) study was designed to evaluate the critical interplay of two key variables for spray-drying using a BUCHI B-290 mini spray dryer: solid load and atomizing spray gas flow. The critical quality attributes (CQAs) of the ASDs, including yield, particle size, morphology, and in vitro release profile, were taken into account to identify the impact of the key variables. The mini-DoE results indicated that a 5% solid load (w/v %) and 35 mm height atomizing spray gas flow were the most optimized parameters. These predefined values were further verified using different formulation compositions, including various polymers (Eudragit L100-55, HPMCAS-MF, PVAP, and PVP-VA64) and drugs (G-F, GEN-A, Indomethacin, and Griseofulvin), a range of drug loading (10 to 40%), and scale (200 mg to 200 g). Using these predefined parameters, all ASD formulations resulted in good yields as well as consistent particle size distribution. This was despite the differences in the formulations, making this a valuable and rapid approach ideal for early development. This strategy of leveraging the preset spray-drying parameters was able to successfully translate into a reproducible and efficient spray-drying platform while also saving material and reducing developmental timelines in early-stage formulation development.
喷雾干燥分散体（SDD）是一种成熟的制造技术，用于制备无定形固体分散体（ASD），可提高难溶性药物的生物利用度。然而，喷雾干燥过程中存在多个因素和众多变量，可能导致漫长的开发时间表和高强度的资源需求，这成为限制临床前阶段喷雾干燥开发的主要障碍。本工作的目的是确定喷雾干燥的优化预设参数，以支持适用于大多数情况而非个别优化的 ASD 的早期开发。首先，设计了一项 mini-DoE（实验设计）研究，以评估使用 BUCHI B-290 迷你喷雾干燥器喷雾干燥的两个关键变量之间的关键相互作用：固体负载和雾化喷雾气体流量。将 ASD 的关键质量属性（CQAs），包括收率、粒径、形态和体外释放曲线，考虑在内，以确定关键变量的影响。mini-DoE 结果表明，5%的固体负载（w/v%）和 35mm 的雾化喷雾气体流量是最优化的参数。这些预定义值使用不同的配方组成进一步验证，包括各种聚合物（Eudragit L100-55、HPMCAS-MF、PVAP 和 PVP-VA64）和药物（G-F、GEN-A、吲哚美辛和灰黄霉素）、一系列药物负载（10%至 40%）和规模（200mg 至 200g）。使用这些预定义参数，所有 ASD 配方都获得了良好的收率和一致的粒径分布。尽管配方存在差异，但这是一种有价值且快速的方法，非常适合早期开发。这种利用预设喷雾干燥参数的策略能够成功转化为可重复且高效的喷雾干燥平台，同时在早期配方开发中节省材料并缩短开发时间。
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