Solid amorphous dispersions are frequently used to improve the solubility and, thus, the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Spray-drying, a well-characterized pharmaceutical unit operation, is ideally suited to producing solid amorphous dispersions due to its rapid drying kinetics. This paper describes a novel flowchart methodology based on fundamental engineering models and state-of-the-art process characterization techniques that ensure that spray-drying process development and scale-up are efficient and require minimal time and API. This methodology offers substantive advantages over traditional process-development methods, which are often empirical and require large quantities of API and long development times. This approach is also in alignment with the current guidance on Pharmaceutical Development Q8(R1). The methodology is used from early formulation-screening activities (involving milligrams of API) through process development and scale-up for early clinical supplies (involving kilograms of API) to commercial manufacturing (involving metric tons of API). It has been used to progress numerous spray-dried dispersion formulations, increasing bioavailability of formulations at preclinical through commercial scales.

中文翻译：

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喷雾干燥工艺开发的基于模型的方法论。

固态无定形分散体经常用于改善溶解性，从而改善难溶性活性药物成分（API）的生物利用度。喷雾干燥是一种众所周知的药物单元操作，由于其快速的干燥动力学，非常适合生产固体无定形分散体。本文介绍了一种基于基本工程模型和最新工艺表征技术的新颖流程图方法，可确保喷雾干燥工艺的开发和规模化是高效的，并且需要最少的时间和API。与传统的过程开发方法相比，这种方法具有实质性的优势，而传统的过程开发方法通常是经验性的，需要大量的API和较长的开发时间。这种方法也与有关药品开发Q8（R1）的当前指南保持一致。从早期的配方筛选活动（涉及API的毫克）到工艺开发和扩大早期临床供应（涉及公斤的API）到商业生产（涉及公吨的API），都使用该方法。它已被用于开发多种喷雾干燥的分散体制剂，从而在临床前到商业规模上提高了制剂的生物利用度。