Browsing Theses and Dissertations School of Pharmacy by Author "Li, Zhili"
Development of a patient inhalation training tool and use of simulated inhalations to study dry powder inhaler performance realistically in vitroLi, Zhili; Dalby, Richard N. (2002)Patients find metered dose inhalers difficult to use correctly. A computerized training tool to detect and immediately respond to common problems, such as, inadequate coordination between inhalation and actuation, was developed. Pressure, force and acceleration transducers mounted on a placebo MDI, and a C program written to acquire these signals, was used to deliver situation-specific, real time feed back on the performance of five volunteers. A computer interface provided pop-up instructions in response to the volunteer's inhalation profile, actuation force, shaking intensity and their temporal relationship. Improvements in technique were realized, and the system proved capable of recording inspiratory profile parameters. A method of reproducing recorded inhalation profiles was validated, and applied to in vitro testing of a Rotahaler dry powder inhaler. The performance of passive DPIs is known to be dependent on inhalation profile, but clinical studies have little power to discriminate the influence of specific breathing patterns on lung deposition. An electronic valve and computerized control system were used to generate a series of simulated inhalation profiles. Four liters of air, at a peak flow rate of 30, 60 or 100 L/min, was drawn through a preloaded Rotahaler. Peak flow was achieved instantaneously (USP method) or linearly approached over 0.1, 0.5, 1, 2 or 3 seconds. The amount and particle size of albuterol and lactose exiting Rotahaler was simultaneously determined by laser diffraction and inertial impaction. Rapidly imposed, higher flow rates drawn through the DPI induced more emptying and smaller emitted drug and carrier particles sizes. The USP method of instantaneously reaching the peak flow rate yielded maximal powder emptying and minimum particle size. Area under the laser obscuration versus time plot was found to correlate to total powder emptying. This relationship was used to demonstrate that most powder leaves a DPI before the peak flow rate is achieved. A correlation between the fine particle fraction of albuterol (obtained from cascade impaction) and the volume mean diameter (of lactose and albuterol) obtained from laser diffraction was established. This work represents a step towards applying realistic inhalation profiles to both established inertial, and more convenient laser based aerosol evaluation techniques.