Purpose

The purpose of this work is to introduce solvent-assisted secondary drying, a method used to accelerate the residual solvent removal from spray dried materials. Spray-drying is used to manufacture amorphous solid dispersions, which enhance the bioavailability of active pharmaceutical ingredients (APIs) with low aqueous solubility. In the spray-drying process, API and excipients are co-dissolved in a volatile organic solvent, atomized into droplets through a nozzle, and introduced to a drying chamber containing heated nitrogen gas. The product dries rapidly to form a powder, but small amounts of residual solvent (typically, 1 to 10 wt%) remain in the product and must be removed in a secondary-drying process. For some spray-dried materials, secondary drying by traditional techniques can take days and requires balancing stability risks with process time.

Methods

Spray-dried polymers were secondary dried, comparing the results for three state-of-the-art methods that employed a jacketed, agitated-vessel dryer: (1) vacuum-only drying, (2) water-assisted drying, or (3) methanol-assisted drying. Samples of material were pulled at various time points and analyzed by gas chromatography (GC) and Karl Fischer (KF) titration to track the drying process.

Results

Model systems were chosen for which secondary drying is slow. For all cases studied, methanol-assisted drying outperformed the vacuum-only and water-assisted drying methods.

Conclusions

The observation that methanol-assisted drying is more effective than the other drying techniques is consistent with the free-volume theory of solvent diffusion in polymers.

中文翻译：

---

喷雾干燥聚合物的溶剂辅助二次干燥。

目的

这项工作的目的是引入溶剂辅助的二次干燥，这是一种用于加快从喷雾干燥材料中去除残留溶剂的方法。喷雾干燥被用于制造无定形固体分散体，其提高了具有低水溶性的活性药物成分（API）的生物利用度。在喷雾干燥过程中，API和赋形剂共溶解在挥发性有机溶剂中，通过喷嘴雾化成液滴，然后引入到包含加热氮气的干燥室中。产品迅速干燥形成粉末，但产品中残留少量残余溶剂（通常为1至10 wt％），必须在二次干燥过程中将其除去。对于某些喷雾干燥的材料，

方法

对喷雾干燥的聚合物进行二次干燥，比较采用夹套，搅拌式容器干燥机的三种最新方法的结果：（1）仅真空干燥，（2）水辅助干燥或（3 ）甲醇辅助干燥。在不同的时间点提取材料样品，并通过气相色谱（GC）和卡尔·费休（KF）滴定进行分析，以追踪干燥过程。

结果

选择二次干燥较慢的模型系统。在所有研究的案例中，甲醇辅助干燥优于纯真空和水辅助干燥方法。

结论

甲醇辅助干燥比其他干燥技术更有效的观察结果与聚合物中溶剂扩散的自由体积理论一致。