Occoris - Self Activating Smart Inhaler

Lead Research Organisation: University of Hertfordshire
Department Name: School of Life and Medical Sciences

Abstract

The global burden of obstructive lung diseases (OLDs) is significant. Almost 300 million individuals worldwide are affected
by asthma and chronic obstructive pulmonary disease is predicted to be the third-leading cause of death by 2020. Drugcontaining
aerosols are the gold-standard therapy in the treatment of OLDs. Drug delivery to the deep lung remains an
unmet challenge using existing products. A key challenge to be addressed is the requirement for delivery of an aerosol that
targets the diseased airways and minimizes throat deposition, the most frequent cause of side-effects from inhalation
therapy.
Existing inhaled therapies have several drawbacks:
1. Nebulizer formulations are suitable for patients with severe OLDs, but they are expensive, difficult to operate, require
electricity and are usually non-portable;
2. Pressurized metered dose inhalers (pMDIs) produce aerosols with a size suitable for targeting the diseased airways
deep in the lung, but are difficult to use correctly, are only suitable for delivering small doses, and between 30 - 60 % of the
drug deposits in the throat;
3. Most dry powder inhalers (DPIs) are passive devices where drug is aerosolized under the force generated when the
patient inhales through the device. OLD patients are often unable to inhale with sufficient force to generate an aerosol
suitable for deposition in the target affected airways, rather than in the upper airways;
4. It is complex to achieve uniformity of dose content and homogeneous lung dosing when manufacturing DPIs, particularly
for high dose drugs such as antibiotics. Advanced formulation and device engineering are required to achieve manufacture
of functional DPI products. Effective devices often require energy input such as electromechanical force, or compressed
air.

Planned Impact

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.

Publications

10 25 50
 
Description We have demonstrated the ability for formulate high dose inhalation products that do not require the use of a large bulking agent through specialist choice of formulation excipients and manufacturing processes.
We have developed a new manufacturing process for the production of inhaled antibiotics with improved shelf-life stability to existing manufacturing strategies.
Exploitation Route We are currently incorporating the formulations developed in this Occoris project to advantage within the INFORM 2020 research collaboration (EP/N025075/1), and into a new PhD collaboration with Harro Hoffliger to advance the findings. The main collaborator (Harro Hoeffliger) will be investigating the behavior of the formulations in a patented manufacturing process (spheronization) as well as incorporating our formulations into their developing dry powder inhaler device. Future publications will require careful phasing to coincide with the industrial collaborators commercialization strategies.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description From our findings on the aerosolization of high-dose formulations containing only inhalable microparticles (without large particle "carrier" lactose mononhydrate diluent), and the the aerosolisation airflow requirements, the industrial partner has redesigned their device design strategy based on the material properties which were identified in the academic project. They have now initiated a new product development stream, which includes a PhD programme supported in the UK, and involves a UK SME as a development partner.
First Year Of Impact 2019
Sector Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Hertfordshire Local Growth Fund 2015
Amount £55,000 (GBP)
Organisation Department for Business, Energy & Industrial Strategy 
Sector Public
Country United Kingdom
Start 03/2016 
End 02/2017
 
Description Inhaled Formulation Excipients Supply 
Organisation DFE Pharma
Department DFE Pharma Netherlands
Country Netherlands 
Sector Private 
PI Contribution Testing of the functional characteristics of DFE Pharma's new engineering formulation excipients.
Collaborator Contribution DFE Pharma is supplying formulation excipients to the INFORM 2020 consortium. In addition, DFE is partnering with the consortium for testing and assessment of its developmental excipient products. Finally DFE Pharma has kindly provided excipient material to employ in the formulation development work for testing in the Occoris device. which we are currently developing at the University of Hertfordshire.
Impact None to date
Start Year 2017
 
Description Occoris Development Team 
Organisation Constantia Flexibles Group GmbH
Country Austria 
Sector Private 
PI Contribution Development of inhaler device technologies, characterisation of pharmaceutical packaging films, physical and chemical testing of formulation and packaging performance.
Collaborator Contribution Harro Hoefliger is commercialising the production of Occoris packaging technologies; Constantia Flexibles is developing and characterising aluminium composite films to support the Occoris technology development.
Impact None to date.
Start Year 2017
 
Description Occoris Development Team 
Organisation Harro Hofliger Packaging Systems Ltd
Country United Kingdom 
Sector Private 
PI Contribution Development of inhaler device technologies, characterisation of pharmaceutical packaging films, physical and chemical testing of formulation and packaging performance.
Collaborator Contribution Harro Hoefliger is commercialising the production of Occoris packaging technologies; Constantia Flexibles is developing and characterising aluminium composite films to support the Occoris technology development.
Impact None to date.
Start Year 2017