In-line technology for assessment of pulmonary drug delivery

• Main Author: Kusmartseva, Olga E.
• Published: Loughborough University 2005
• Subjects: 615.6
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.488539

The 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.