Creation and validation of an enhanced in vitro model of the lungs

The increasing prominence of pulmonary drug delivery for local and systemic treatments coupled with the complex lung structure and the numerous factors affecting the pulmonary delivery of drugs has necessitated extensive research on this drug delivery route. The research mostly includes studies on characterization of aerosolized formulations in terms of their aerodynamic properties and particle size, and also in vitro, ex vivo and in vivo evaluation of the efficacy and the pharmacokinetic and pharmacodynamic properties of the formulations. However, a need is felt for improved models of aerosol testing, which closely simulate the aerosolization of the formulation in the lungs and in which two or more parameters for aerosol characterization can be simultaneously tested. This Master’s thesis describes the development and validation of an improved in vitro model of the diseased lung which can be used for accurate evaluation of inhaled formulations.|An enhanced in vitro model of the lung was created by carrying out modifications in the collection cups of the Next Generation Impactor (NGI) to allow incorporation of bacterial cultures for evaluation of formulation efficacy. The regular collection cup in the stage 4 of the NGI was replaced with a deep collection cup for incorporating bacterial cultures without affecting the critical impaction distance. Various modifications using agar plates, polymer as a collection surface and liquid collection surface were carried out. Theophylline solution was nebulized in both the regular and modified NGI and the particle size distribution and aerodynamic parameters such as Mass Median Aerodynamic Diameter (MMAD), Geometric Standard Deviation (GSD) and Fine Particle Fraction (FPF) in both the models were compared. The modification using liquid collection surface was chosen for further studies as the parameters obtained in the modified NGI modified did not display any statistically significant difference from those obtained in the regular NGI.|Ceftazidime was chosen as the antibiotic of choice because of its broad spectrum of activity and potential use in the treatment of pneumonia. Escherechia coli K12 MG 1655 was chosen for the bacterial studies because of its susceptibility to antibiotics, allowing for unbiased evaluation of the modified NGI performance. The sterility testing in the modified NGI in the laboratory environment indicated prevention of environmental contamination in the NGI. The airflow in the NGI and the excepients of ceftazidime formulation did not cause any reduction of bacterial count in the modified NGI. Ceftazidime solution nebulized in the modified NGI was able to completely inhibit bacterial growth.|The selected modification in the NGI allowed for testing of aerosolized antibiotic formulation efficacy. However, further studies need to be performed to widen the scope of the application of the modified NGI as an enhanced model for in vitro aerosol testing.

Grantor dc:publisher

Creighton University

Year dc:date.issued

2012

Author dc:creator

• Gharse, Sachin R.

Advisor dc:contributor.advisor

• Tolman, Justin A.

Statement dc:rights

• Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10504/31224

OAI identifier oai:identifier

oai:cdr.creighton.edu:10504/31224