A Novel and Improved Commercially Viable, Cost -Effective Manufacturing Process for Fixed Dose Combination Dry Powder Inhaler Formulations

用于固定剂量组合干粉吸入剂配方的新颖且改进的商业可行的、具有成本效益的制造工艺

• 批准号: 104523
• 金额: $ 48.86万
• 依托单位: ASTON PARTICLE TECHNOLOGIES LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=104523
• 关键词: Novel; Improved; Commercially; Viable; Cost

At the present time there are few, if any, manufacturing processes for particle surface modification that do not adversely affect the innate properties of the core particles. State-of-the-art blending technologies for DPIs, e.g. high shear or turbula mixing, often are unsuitable for processing poorly stable APIs and even when suitable, create highly variable product outputs. This becomes even more complex when combinations containing more than one API are to be created. This project is targeted to deliver improved and commercially viable cost-effective processes for manufacture of formulations of small molecule APIs that are already available as Fixed Dose Combination (FDC) DPI medicines. These products have proven to be very difficult to turn into generic medicines until now. Aston Particle Technologies (APT) Ltd. has created a novel dry particle coating process, newly trademarked as APT-Hale(tm), which could be a game-changer in this regard. The process has many unique characteristics which have been confirmed with single API formulations. It operates at ambient temperature, requires the use of no volatile organic compounds (VOCs) or solvents, generates no heat and causes no particle attrition. It can handle APIs with problematic properties, such as high charge / high charge retentiveness, high cohesivity or acute moisture sensitivity. It can be applied equally to poorly stable APIs as to those that are robust. It has already been successfully used with readily available 'off the shelf' APIs and excipients with no pre-treatment. The process operates through control of a small number of critical processing parameters which create a fluidised state in dry nitrogen, in which every fine particle is firstly fully wetted by the dispersion gas and then adsorbed onto the coarser carrier particles. It is a primary aim of this project to validate the broad applicability of the process by creating FDC DPI formulations that can be progressed as credible substitutable generics for the market-leading, innovator products. In doing so, a range of established, off patent APIs will be investigated in combination. Application of this simple and relatively 'easy to implement' platform for development and scale up could eventually lead to registration of a suite of generic FDC inhalers that will meet the requirements of prescriber, payer and patient alike. If this project is successful, this platform technology will be utilised in the longer term not only in the development of generic combination formulations but also of those containing new chemical entities.

目前，几乎没有（如果有的话）不对核颗粒的固有性质产生不利影响的颗粒表面改性的制造方法。DPI的最新混合技术，例如高剪切或双螺杆混合，通常不适合加工稳定性差的API，即使在合适的情况下，也会产生高度可变的产品输出。当要创建包含多个API的组合时，这变得更加复杂。该项目旨在提供改进的、商业上可行的、具有成本效益的工艺，用于生产已经作为固定剂量复方（FDC）DPI药物提供的小分子API制剂。事实证明，到目前为止，这些产品很难变成仿制药。阿斯顿粒子技术（APT）有限公司创造了一种新的干颗粒涂层工艺，新商标为APT-Hale（tm），这可能是一个游戏规则改变这方面。该工艺具有许多独特的特征，这些特征已通过单一API制剂得到证实。它在环境温度下运行，不需要使用挥发性有机化合物（VOC）或溶剂，不产生热量，也不会引起颗粒磨损。它可以处理具有问题性质的原料药，如高电荷/高电荷保持性，高凝聚性或急性湿敏性。它同样适用于稳定性差的API和健壮的API。它已经成功地与现成的API和辅料一起使用，无需预处理。该方法通过控制少量关键工艺参数来操作，这些参数在干燥氮气中产生流化状态，其中每个细颗粒首先被分散气体完全润湿，然后吸附到较粗的载体颗粒上。该项目的主要目的是通过创建FDC DPI制剂来验证该工艺的广泛适用性，这些制剂可以作为市场领先的创新产品的可靠替代仿制药进行开发。在此过程中，将对一系列已建立的非专利API进行联合研究。应用这种简单且相对“易于实施”的开发和规模扩大平台，最终可能会导致一套通用FDC吸入器的注册，这些吸入器将满足处方者、付款人和患者的要求。如果该项目取得成功，该平台技术不仅将长期用于开发通用组合制剂，还将用于开发含有新化学实体的制剂。