The UCL School of Pharmacy has developed new techniques for assessing materials in inhalation products, leading to improvements in the design, control and manufacture of those products. The type of assessment developed at UCL is now a requirement for licensing of powder inhalation medicines both in the USA and across Europe.
By 2017 the value of the global market for inhalation device is forecast to reach some $20 billion. These devices already provide essential – and often life-saving – therapy for the management of a range of diseases, including asthma and chronic obstructive pulmonary disease. New inhalation therapies are, moreover, also in development for the treatment of infection and gene therapy for cystic fibrosis, as are many systemic delivery therapies for conditions such as migraine, sexual dysfunction and pain control.
The efficacy of inhalation devices relies on their capacity to reliably deliver the correct quantity of the treatment drug to the right part (or parts) of the lungs. To achieve this, the drugs and excipient powders used for inhalation aerosols must be of a very specific size, and processing techniques such as micronisation – used to reduce the average diameter of a solid material’s particles – are often employed to meet this requirement. But whilst these techniques help control particle properties, there is a well-recognised danger that they may also cause unforeseen changes in performance, allowing seemingly identical materials to perform very differently. Given the ever-greater market and range of applications for them, it is increasingly important to understand and control these inhalation products, including by reducing or eliminating these batch-to-batch variations in performance.
Many researchers have made significant contributions to this work in my lab at the School of Pharmacy. It is thanks to all of them that better products can be made and that has a direct impact on the health and well being of the public. I am delighted to have seen this work applied during my time at Pharmaterials Ltd and as I travel to other companies around the world. – Professor Graham Buckton
A research group led by Professor Graham Buckton (UCL School of Pharmacy) has spent the last 20 years seeking to identify, quantify and understand the reasons behind these performance changes, focusing particularly on the potentially significant effects of subtle changes in the surface properties of drugs and powders. Their work has especially helped identify the impacts of surface amorphisation – the presence of less crystalline material at the surface of a particle. It has demonstrated both that this amorphism can be generated during the micronisation process and that the presence of amorphous content produces variability in the manufacture and performance of inhalation products. Since inhalation particles are inevitably small, their large surface-area-to-volume ratio makes them very sensitive to such changes in surface properties. However, because the surface constitutes only a very small proportion of the bulk of a solid material, the detection of such changes is difficult. Professor Buckton’s group responded to this difficulty by developing sophisticated and sensitive new methodologies allowing the detection of amorphous material in quantities well under 1% of the total particle mass. Those methods have since been very widely used in, and made a vital contribution to, both academic research and industry practice.
By allowing the reliable quantification of amorphous content in micronised powders, the methods have profoundly influenced and improved industrial practices associated with quality control of powders for inhalation, which include steps intended to help reduce batch-to-batch variations in drug performance. The research has also had a very important influence on regulatory processes, such that it is now a requirement in both Europe and the USA that inhalation materials are tested for amorphous content prior to licensing.
As well as influencing industrial practice, the UCL work was central to the creation in 2000 of Pharmaterials Ltd, a spin-out company providing specialist consultancy and expertise to pharmaceutical and related companies of many types, including active ingredient manufacturers, SME development companies and large multinationals. The data generated by Pharmaterials are also used in the development of product specifications and are submitted to regulatory authorities around the world. By 2013 Pharmaterials had grown to employ 38 people, generating an annual turnover of around £3 million.