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

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.