Show simple item record

dc.contributor.advisorChrystyn, Henry
dc.contributor.advisorAssi, Khaled H.
dc.contributor.authorIbn Yakubu, Sani*
dc.date.accessioned2011-04-04T15:41:29Z
dc.date.available2011-04-04T15:41:29Z
dc.date.issued2011-04-04
dc.identifier.urihttp://hdl.handle.net/10454/4861
dc.description.abstractCurrently available dry powder inhalers (DPIs) for drug delivery to the lungs require turbulent energy to generate and disperse aerosol particles in the respirable range ¿5¿m during inhalation. The patient's inspiratory effort together with the resistance inside the device creates this energy. Different inhalers provide varying degrees of resistance to inhalation flow and require different inhalation techniques for the generation and delivery of drug fine particles in respirable size range to the lungs. The aim of this research programme was to identify the influence of inhalation flow, inhalation volume and the number of inhalations per dose on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of the salbutamol Accuhaler®, Easyhaler®, and Clickhaler® and the terbutaline Turbuhaler® DPIs. A high-performance liquid chromatography method for the assay of salbutamol sulphate and terbutaline sulphate in aqueous samples was modified and accordingly validated. In-vitro dose emission of the four different DPIs was measured using the pharmacopoeia method with modifications to simulate varying inhalation flows within patient and between patients. The ranges of the total emitted dose (% nominal dose) at the inhalation flow range of 10 - 60 Lmin-1, following one and two inhalations per metered dose for 2L and 4L inhaled volumes were as follows: the Accuhaler (52.64- 85.11; 61.88-85.11 and 59.23-85.11; 62.81-85.11); the Easyhaler (68.35-91.99; 79.94-91.99 and 73.83-92.51; 80.40-92.51); the Clickhaler (46.55-96.49; 51.12-96.49 and 51.18-101.39; 59.71-101.39) as well as the Turbuhaler (46.08-88.13; 51.95-88.13 and 48.05-89.22; 48.64-89.22). The results highlight that the four inhalers have flow-dependent dose emission property to a varying degree using 2L and 4 L inhaled volumes. There was no significant difference in the total emitted dose between a 2L inhaled volume and a 4L inhaled volume at each inhalation flow. Furthermore, the total emitted dose from the Easyhaler®, Clickhaler®, and Turbuhaler® was significantly (p¿0.001) greater with two inhalations than one inhalation per metered dose across the range of inhalation flow (10 ¿ 60) Lmin-1. This effect was only observed at inhalation flow less than 30 Lmin-1 with the Accuhaler®. Overall there is a significant difference in the total emitted dose. The ex-vivo dose emission of the four different DPIs has been determined using the In- Check Dial device to train twelve non-smoking healthy adult volunteers to inhale at slow (30 Lmin-1) and fast (60 L min-1) inhalation flows through the device with its dial set corresponding to each inhaler. Subsequently each volunteer inhaled at the trained inhalation flows through each active inhaler. The local ethics committee approval was obtained prior to the study and all volunteers gave signed informed consent. The results obtained demonstrate that the studied inhalers have flow-dependent dose emission, thereby enhancing confidence in the use of the In-Check Dial® to identify a patient¿s inhalation flows through a variety of DPIs. Also the total emitted dose determined by ex-vivo methodology was significantly (p¿0.05) greater with two inhalations than one inhalation per metered dose. The results of the in-vitro aerodynamic dose emission characteristics highlight that the fine particle dose (FPD) from the four studied inhalers is flow dependent. Also the minimum inhalation flow to generate the (FPD) with the appropriate characteristics for lung deposition has been identified to be 20 L min-1 for the Accuhaler®, Easyhaler® and Clickhaler®, while that for the Turbuhaler® is about 30 L min-1. Also the inhalation volume above 2L and the number of inhalations for each dose have respectively no significant (p¿0.05) influence on the FPD emitted from the four studied inhalers. The results support the present instructions to patients using these inhalers to inhale once for each dose as fast as they can.en_US
dc.language.isoenen_US
dc.rights© 2009 Yakubu, S. I. This work is licensed under a Creative Commons Attribution-Non-Commercial-Share-Alike License (http://creativecommons.org/licenses/by-nc-nd/2.0/uk).en_US
dc.subjectDose emissionen_US
dc.subjectEx-vivoen_US
dc.subjectIn-vitroen_US
dc.subjectAerodynamic characteristicsen_US
dc.subjectInhalation flowen_US
dc.subjectInhalation volumeen_US
dc.subjectDry powder inhalersen_US
dc.titleInvestigations to identify the influence of the inhalation manoeuvre on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of dry powder inhalers: Studies to identify the influence of inhalation flow, inhalation volume and the number of inhalations per dose on the ex-vivo dose emission and the in-vitro aerodynamic dose emission characteristics of dry powder inhalers.en_US
dc.type.qualificationleveldoctoralen_US
dc.publisher.institutionUniversity of Bradfordeng
dc.publisher.departmentInstitute of Pharmaceutical Innovationen_US
dc.typeThesiseng
dc.type.qualificationnamePhDen_US
dc.date.awarded2009
refterms.dateFOA2018-07-19T04:49:33Z


Item file(s)

Thumbnail
Name:
Sani`s+Thesis.pdf
Size:
6.440Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record