Spray Drying as a One-Step Formulation Process

微喷雾干燥作为一步制剂工艺为少量患者（其中n可以=1）生产定制药物在技术和经济上都具有挑战性。固体分散体的大规模生产是多阶段的且效率低。增材制造提供了一种制造单一定制剂型的解决方案，但可能经常需要可能特定于每种治疗剂的专用油墨。这可能会限制其快速原型化和探索制剂空间的能力，而且会给监管批准带来重大问题和障碍。喷雾干燥工艺是一种长期建立的、批准的连续制造工艺，通常用于生产无定形固体分散体，用于提高难溶性药物的口服生物利用度。这里的概念是将喷雾干燥工艺按比例缩小到能够一次生产单个剂量单位的无定形固体分散体以及剂型所需的任何其他成分的程度。这可以在生产规模上运行，在单个步骤中单独生产许多剂型，目前需要7个或更多个步骤。或者，也可以小规模生产，按需生产溶解性差的药物的个性化片剂。喷雾干燥在这里受到青睐，因为众所周知，它是一种高度可控和可重复的工艺，因此非常适合：-扩大规模快速一步生产复杂片剂。-缩小规模，实现个性化片剂生产。该项目将为少量患者开发灵活的喷雾干燥生产工艺平台，提供生产定制微胶囊粉末的能力，用于口服剂型，如胶囊，加入微针阵列，与蛋白质混合等。我们将研究喷雾干燥工艺背后的工程和物理原理，特别是使用诸如表面张力和粘度的性质的物理化学表征来揭示这些如何能够告知流体的设计和工程，（微观和宏观）流动、喷嘴几何形状、气体流动、温度、流动几何形状，我们将设计和开发一种小型化喷雾器-干燥原型，并使用此和从材料及其在装置中的行为的表征中获得的知识来生成可用于配制各种API的个性化剂型的设计规则。微喷雾干燥的材料将与传统的小规模生产系统进行比较。我们灵活的微喷雾干燥平台的一个潜在应用是个性化的联合化疗。联合治疗是将两种或多种治疗剂组合的治疗方式，是癌症治疗的基石。与单一治疗方法相比，抗癌药物的合并提高了疗效，因为它以特有的协同或相加方式靶向关键途径。现场和按需定制个性化组合疗法的能力可节省成本和时间，并将对治疗方案的交付产生重大影响。快速小规模生产还将加快新制剂的开发，无论是用于新活性物质还是用于新适应症。项目与制药工艺工程和先进产品设计相结合

Micro Spray Drying as a One Step Formulation ProcessThe manufacture of tailored drugs for small numbers of patients (where n could be =1) is challenging both technically and economically. The large-scale manufacture of solid dispersions is multi-stage and inefficient. Additive manufacturing offers one solution to the manufacture of single tailored dosage form but can suffer from often requiring specialized inks that maybe specific to each therapeutic. Such can limit its ability to rapidly prototype and explore formulation-space, and moreover creates significant issues and barriers to regulatory approval.The spray drying process is a long-established, approved continuous manufacturing process that is routinely used for the production of amorphous solid dispersions, used to enhance the oral bioavailability of poorly soluble drugs. The concept here is to scale down the spray drying process to the point of being able to produce amorphous solid dispersions for a single dosage unit at a time, together with the any other constituents necessary for the dosage form.This could be run at a manufacturing scale, producing many dosage forms individually in a single step, where 7 or more steps are currently required. Or, this could be run at a small scale, producing personalised tablets of poorly soluble drugs on demand.Spray-drying is favoured here as it is known to be a highly controllable and repeatable process, hence it is ideally suited to:- SCALE UP for rapid single step manufacture of complex tablets.- SCALE DOWN to enable personalised tablet manufacture.The project will develop a flexible miniaturised spray drying manufacturing process platform for small quantities of patients offering the capability to manufacture tailored micro-encapsulated powder, for use in oral dosage forms such as capsules, incorporation into micro needle arrays, blending with proteins, etc.We will study the engineering and physical principles behind the spray-drying process, in particular using physicochemical characterization of properties such as surface tension and viscosity to reveal how these can inform the design and engineering of the fluidic (micro and macro) flow, nozzle geometry, gas flow, temperature, flow geometry, etc. We will design and develop a working miniaturized spray-drying prototype and use this and the knowledge gained from the characterization of the materials and their behaviour in the device to generate design rules that can be used to formulate personalized dosage forms of a variety of APIs. Micro-spray dried material will be compared to that produced using a traditional small-scale manufacture system.One potential application for our flexible micro-spray drying platform would be for personalised combination chemotherapy. Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. The ability to potentially formulate, on site and on demand, personalized combination therapies offers saving in cost and time, and stands to make a significant impact in the delivery of therapies.Rapid small-scale manufacture would also quicken the development of new formulations, either for new actives or for new indications.Project aligned to Pharmaceutical Process Engineering and Advanced Product Design