Development and Evaluation of a Small Volume Liquid Impaction Surface (SVLIS) in the Next Generation Impactor (NGI)

The growing popularity of inhalation as a route of administration for local action in the lungs as well as systemic effects has necessitated the development of in vitro models for studying the deposition, dissolution and absorption of orally inhaled drug formulations. Models that integrate the study of at least two of these processes would be better able to simulate conditions in vivo. This thesis describes the design and evaluation of a Small Volume Liquid Impaction Surface (SVLIS) in the Next Generation Impactor (NGI), a cascade impactor for evaluation of aerodynamic particle size distribution. This SVLIS modified NGI allowed for incorporation of lung cell cultures or drug dissolution of orally inhaled powders following aerosolization.|A custom SVLIS was designed to accommodate a liquid volume of 5 mL for incorporation in the NGI stages using the gravimetric cup. It allowed the growth of cells in a way as to mimic the thin layer of fluid lining the lung. A549 cells were grown on the SVLIS and saline administration through the NGI did not adversely affect the cells grown on the SVLIS; though airflow alone decreased cell survival.|The SVLIS was incorporated in various stages of the NGI to study the effect of the modification on aerosol deposition patterns of a nebulized model drug. Though significant differences were seen in deposition at some of the stages, the deposition patterns and aerodynamic properties of aerosols obtained in the SVLIS at stage 4 did not differ from those in the unmodified NGI. A model dry powder for oral inhalation was aerosolized through the stage 4 SVLIS modified NGI using a DPI, but the deposition at stage 4 was seen to be different from that in unmodified NGI. A preliminary dissolution study of powdered theophylline was performed using the SVLIS modified NGI, which showed that the SVLIS could be potentially used in in vitro dissolution models for inhaled drugs. The results from all the studies showed that the SVLIS has potential applications in studying inhaled drug absorption and dissolution following deposition in the NGI.

Grantor dc:publisher

Creighton University

Year dc:date.issued

2014

Author dc:creator

• Navalkar, Nikita Deepak

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/10504/62863

OAI identifier oai:identifier

oai:cdr.creighton.edu:10504/62863