Thesis-2005-Kusmartseva.pdf (26.85 MB)
In-line technology for assessment of pulmonary drug delivery
thesis
posted on 2013-08-08, 13:47 authored by Olga E. KusmartsevaThe World Health Organisation estimates that 100 million people worldwide suffer
from asthma. Chronic obstructive pulmonary disease (COPD) is the fourth leading
cause of death worldwide. Pulmonary drug delivery is widely accepted as the firstchoice
method for the treatment of respiratory diseases by glucocorticosteroids.
Delivering these drugs to the lung by inhalation has many advantages in comparison
to the same drug delivered orally. These include rapid onset of action, reduced dose
and minimised side effects such as adrenal suppression, electrolyte imbalance,
muscle weakness and growth retardation in children. Pulmonary drug delivery is also
increasingly used for pain-controlling therapies and for administration of
medications which are difficult to formulate orally such as proteins and peptides.
The advantages of delivering drugs to the lung are undisputed, however, there are
practical challenges still remaining to achieve repeatable and accurate dose delivery
to the deep lung. An enabling technology for actuation-by-actuation, in-line
measurement of pulmonary drug delivery is part of this greater challenge. The
aerosol particles can penetrate into the deep lung only if their aerodynamic size is in
the narrow range of O.5μm to 5μm. The larger particles contribute to the
oropharyngeal deposition diminishing the pulmonary-delivery advantages, and the
smaller particles are exhaled. Particles of this size-range agglomerate easily through
adhesion/cohesion interactions. Agglomerates have to disperse in the patient's
inspiration flow. Therefore, the respirable dose and therapeutic efficacy depend on
the drug formulation, the inhalation device, the ambient conditions and also heavily
rely on the patient's inspiratory effort, which is highly variable. An ability to assess
the efficacy of the pulmonary delivery in-line with a patient will ultimately improve
the effectiveness and efficiency of medical therapy.
This thesis presents a novel optical technology for non-invasive and in-line
measurement of the respirable cloud during pulmonary drug delivery. The
technology can be used as a stand-alone instrument, in conjunction with standard
laboratory analytic apparatus and ultimately in-line with a patient. It is shown how
the technology concept is based on the Mie theory for light scattering by particles
and on the Lambert-Beer law for light extinction by a turbid medium. A prototype
device is developed to implement this concept and a series of experimental
investigations are conducted to evaluate the feasibility of the approach. Comparisons
between the novel in-line technology and conventional in vitro measurements using
physical chemistry apparatus suggest that the approach can become a useful enabling
technology in pulmonary drug delivery assessment.
History
School
- Mechanical, Electrical and Manufacturing Engineering
Publisher
© Olga Evgenievna KusmartsevaPublication date
2005Notes
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.EThOS Persistent ID
uk.bl.ethos.488539Language
- en