Occoris - Self Activating Smart Inhaler

The ability to target lung deposition to the diseased airways is influenced by the patient's cognitive ability to handle the
device correctly, his/her inspiratory profile, and the mechanism of aerosolization of the inhaler. This project focuses on the
development of a novel aerosol generation device called Occoris. Unlike conventional pMDIs, Occoris has no need for
propellants and is recyclable. Similar to DPIs, the aerosol is generated on-demand by the patient. However, because the
drug formulation is pre-packaged in pressurized blisters, the aerosolization is self-activating and is not driven by a forceful
inhalation. When the patient inhales, the blister ruptures, and releases a fine aerosol of drug suitable for deep lung
inhalation. Occoris therefore has potential for:
1. Coordination of drug delivery with inhalation;
2. Minimized throat deposition, compared to pMDIs (even breath-actuated pMDIs);
3. Minimized pulmonary function-derived variability of lung deposition between patients;
4. Consistency of aerosol dose and properties for high-dose DPI products.
In this research programme, we will seek to develop a mechanism to target drug aerosols to diseased regions of the lung
through controlling patient's inspiratory flow rate and the release rate of aerosol particles during an inhalation cycle. This
unique achievement for DPI drug delivery derives from the novel aerosolization mechanism of the Occoris blister design.
Aerosol generation will be studied using a human inhalation simulator to reproduce inhalation profiles recorded from OLD
patients. Drug formulations will be engineered to achieve high dispersibility in studies supported by the development of
advanced analytical methods that test for chemical stability and compatibility with Occoris components. Blister packing
components will be engineered using air-permeable fibre meshes to support the formulations within aluminium blisters that
are designed to rupture when a patient inhales. The knowledge gained from these studies will be translated into products
that minimize throat deposition and maximize deep lung targeting of therapeutic aerosols for the treatment of lung
diseases.

This research has the goal of improving our understanding of drug delivery to the lungs. This will have significant impact on
global pharmaceutical regulation by addressing several knowledge gaps currently hindering successful assessment and
introduction of rival (but bioequivalent) generic inhalation products that will decrease the costs of patient care. It is
anticipated that the translation of the findings into a clinically-exploitable inhaler device could lead to impacts in the
treatment of asthma, chronic obstructive pulmonary disease (COPD) and respiratory infection. Pharmacotherapy of
obstructive lung diseases (OLDs), although successful, has failed to advance significant improvements in mortality and
morbidity [1]. Considerable societal and economic impacts could be advanced by improving clinical treatments.
Societal:
Asthma and COPD are significant causes of mortality and morbidity in the UK with far-reaching societal impacts. In the UK
alone, 900,000 individuals were diagnosed with COPD in 2004 [2] and almost 30,000 people in the UK died from COPD
conditions in 2010 [3]. As a global problem, COPD is expected to be the third-leading cause of death by 2020 [4]. An
estimated 300 million individuals worldwide are affected by asthma [5], 5.2 million people in the UK alone [7]. Worldwide,
asthma deaths are predicted to exceed 180,000 per annum [6]. Poor management of OLDs has an enormous effect on the
well-being of sufferers and the community. 250 million disability adjusted life years are lost to poorly-controlled asthma [5],
whilst 25 % of asthma patients in Western Europe require an emergency doctor's visit every year [8]. Poorly-controlled
COPD results in 1-in-8 hospital admissions [9]. In all, OLDs are associated reduced quality of life including joblessness
[10], loss of earnings [11], impaired study performance, exercise tolerance and socio-sexual relationships [12]. Translation
of improved drug delivery technologies into the clinic after this programme would lead to improved quality of life for many.
Economic:
Treatment costs to the health service and the wider economy of ineffective management (including hospitalisation) have
been estimated. The combined direct and indirect cost of COPD to the National Health Service is £1 billion per annum [2],
whilst the costs of asthma were estimated at £750 million [9]. The impact on the wider economy is also substantial: 21.9
million workdays were lost in 1994-5 due to COPD [2], and 12.7 million workdays are lost annually to asthma symptoms at
an estimated economic cost of £1.2 billion [7]. It is clear improvements in clinical treatments could bring significant
economic gain.