Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494185
Title: Electrostatic charge interactions in pharmaceutical dry powder aerosols
Author: Peart, Joanne
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 1996
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Abstract:
Dry powders for inhalation, although clinically effective, tend to be inefficient in terms of the extent and reproducibility of drug delivery. In part at least this is due to an inadequate understanding of the relevant particle-particle interactions between drug and drug, and drug and carrier. Electrostatic charge interactions are one of several factors influencing the overall efficiency of an inhalation powder. The practical significance of such interactions is considered to be critical in every aspect of the powder formulation, including the formation of an ordered mix and, more importantly, the timely disruption of drug - carrier agglomerates, allowing the reproducible delivery of respirable particles. The principal aim of this study was to provide a more fundamental understanding of electrostatic interactions of poured, packed and aerosolised powders for inhalation. Electrostatic properties of drug and excipient powders were studied using a deep Faraday pail static charge detector. The surface charge developed when adhered drug particles were detached from carrier particles was investigated using two dynamic measurement systems: a) an Airstream Faraday cage, and b) a differential charge-to-mass test system, The electric field attributable to the particle cloud generated by a dry powder inhaler was assessed using a fieldmeter, located at the base of a specially constructed flow tube, through which aerosolised particles were drawn. Characterisation of the electrostatic properties of the respirable fraction of the aerosol generated by high efficiency and commercial inhalers was also achieved. Adhesion forces between drug and carrier particles were measured using a modified centrifuge system. Deposition characteristics of powder mixes were studied using an invitro pharmacopoeial method. Hypotheses relating to particle interactions were established from the data obtained. Electrostatic characterisation of powders following detachment from carrier surfaces showed that they exhibit charges of increased magnitude, and in some cases opposite polarity to those observed following contact. Dynamic charge measurements were considered much more relevant to the performance of dry powder formulations for inhalation than corresponding static determinations. Aerosols generated from dry powders for inhalation were shown to exhibit bipolar charging characteristics, which could result in reagglomeration of charged aerosol particles, and contribute to the reduced efficiency of these systems. Aerosol properties were found to be dependent upon the physical and chemical properties of the material studied and the construction and deaggregation mechanism of the dry powder inhaler (DPI) device. A combination of centrifugation, in-vitro deposition studies using the twin stage impinger (TSI) and electrostatic detachment charges indicated the relative contribution of centrifugal and electrostatic elements toward the deaggregation of drug-carrier complexes in dry powder formulations for inhalation. Good correlation was demonstrated between electrostatic detachment charge measurements and TSI deposition studies for binary and ternary powder blends. In-vitro performance characteristics of dry powder formulations were found to improve upon the addition of ternary and quaternary components. A 'chain breaker' theory has been proposed for the mechanism of interaction between carrier, drug, ternary and quaternary components of the attached chain of constituents, based upon their electrostatic characteristics.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.494185  DOI: Not available
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