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PHARMACEUTICAL PARTICLES FOR PULMONARY DELIVERY PRODUCED
USING A SUPERCRITICAL FLUID PROCESS
by
Yong Ho Kim
____________________________________________________________________
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfilment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(CHEMICAL ENGINEERING)
August 2008
Copyright 2008 Yong Ho Kim
Object Description
| Title | Pharmaceutical particles for pulmonary delivery produced using a supercritical fluid process |
| Author | Kim, Yong Ho |
| Author email | yonghkim@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Chemical Engineering |
| School | Viterbi School of Engineering |
| Date defended/completed | 2008-06-03 |
| Date submitted | 2008 |
| Restricted until | Restricted until 31 July 2010. |
| Date published | 2010-07-31 |
| Advisor (committee chair) | Shing, Katherine |
| Advisor (committee member) |
Chang, Wenji Victor Sioutas, Constantinos |
| Abstract | The physical properties of solid pharmaceutical particles used in pulmonary delivery must, at the minimum, meet the following stringent conditions; the particles must be in the appropriate size range (1~5micron in aerodynamic diameter); there should be minimal agglomeration and their deposition profile in the pulmonary region must be consistent. In this study we used a CO2-based aerosol solvent extraction system (ASES), one of the supercritical fluid techniques, to prepare particles composed of small- or large-molecule drugs that are appropriate for pulmonary delivery.; In the case of small-molecule drug particles, we studied the micronization of ipratropium bromide (IB) and terbutaline sulphate (TS), and examined the effect of varying operating conditions on particle morphology. The results indicate that the size and morphology of the microparticles were most sensitive to solvent choice. We also studied the improvement in aerosolization properties when an appropriate additive (albumin) was added. The results indicate that the IB and TS particles with albumin were more spherical, less cohesive and less agglomerated in air flow, thus expected to lead to more effective and consistent lung deposition.; In the case of large-molecule drug particles, insulin was micronized with appropriate stabilizers and absorption enhancers. Of particular interest in this study was the insulin particle shape and whether processing affects the stability and activity of the insulin. With respect to inhaled insulin particles with stabilizers, insulin/mannitol/trehalose particles were relatively uniform, more spherical, less cohesive, and less agglomerated in air flow, when compared to insulin/mannitol particles which formed irregular and needle-shaped particles. Furthermore, the insulin particle mophology was highly influenced by the addition of the absorption enhancer. In the present study, the use of cyclodextrin and maltoside was suitable to produce inhaled insulin particles which showed relatively spherical-shaped and uniformed particles. The experimental results of insulin stability indicate that the secondary structures of insulin particles were not influenced by the ASES process but slightly enhanced by the addition of the stabilizers. Overall, this study highlights the ASES process can be a valuable technique for producing micron-size pharmaceutical particles suited to pulmonary delivery. |
| Keyword | supercritical antisolvent process; pulmonary drug delivery; insulin; particle micronization |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m1480 |
| Rights | Kim, Yong Ho |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Kim-20080731 |
| Archival file | uscthesesreloadpub_Volume29/etd-Kim-20080731.pdf |
Description
| Title | Page 1 |
| Full text | PHARMACEUTICAL PARTICLES FOR PULMONARY DELIVERY PRODUCED USING A SUPERCRITICAL FLUID PROCESS by Yong Ho Kim ____________________________________________________________________ A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfilment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (CHEMICAL ENGINEERING) August 2008 Copyright 2008 Yong Ho Kim |
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