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Developing microcomposite pharmaceutical materials using dense gas technique
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Text
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Title
Developing microcomposite pharmaceutical materials using dense gas technique
Identifier
ETD_1233
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http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000050475
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eng
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theses
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Chemistry and Chemical Biology
Subject
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Topic
Drug carriers (Pharmacy)
Abstract
Micronized particulate pharmaceutical materials prepared using dense gas antisolvent precipitation is of great advantage over traditional micronization techniques in terms of particle size distribution and reproducibility. Our work shows that spherical particles with different degrees of agglomeration can be produced under mild operating conditions. These results stimulate further studies on the structure-property relationship of the precipitates.
Preliminarily, we performed dense gas antisolvent precipitation on a number of polymers of pharmaceutical interest, including poly(DTE carbonate) and polyvinylpyrrolidone (PVP) with different molecular weights. We explored the effect of experimental conditions on the particle size and morphology. For poly (desamino tyrosyl-tyrosine alkyl ester carbonate) [poly(DTE carbonate)], its microparticles with controlled size could be applied in the field of tissue engineering, which could facilitate better exertion of the biochemical functions of this biodegradable polymer. On the other hand, PVPs are common excipients widely used in pharmaceutical formulation development. Physicochemical properties of both types of polymers provide flexibility of their application. Their precipitation by dense gas as antisolvent provided informative data for subsequent experiment of forming solid dispersions.
Solid dispersions were prepared by precipitation of PVP with several pharmaceutical compounds using dense gas carbon dioxide as antisolvent. We focused on the morphology and particle size control of the products for the first two model drugs, prednisolone and its acetate salt, and then we prepared solid dispersions of a nonsteroidal anti-inflammatory drug, piroxicam. Microcrystals or microspheres were formed where the drug was amorphously dispersed in the polymeric matrix, with drug loadings dependent on initial drug-polymer weight ratios. The existence of interaction between the drug and polymer was confirmed through characterization of their physicochemical properties. The dissolution profiles of solid dispersions showed significant improvement in the dissolution rate of piroxicam compared with their corresponding physical mixtures and plain drug. These results manifest the great potential of this dense gas technique in improving bioavailability of water-insoluble pharmaceutical substances.
Preliminarily, we performed dense gas antisolvent precipitation on a number of polymers of pharmaceutical interest, including poly(DTE carbonate) and polyvinylpyrrolidone (PVP) with different molecular weights. We explored the effect of experimental conditions on the particle size and morphology. For poly (desamino tyrosyl-tyrosine alkyl ester carbonate) [poly(DTE carbonate)], its microparticles with controlled size could be applied in the field of tissue engineering, which could facilitate better exertion of the biochemical functions of this biodegradable polymer. On the other hand, PVPs are common excipients widely used in pharmaceutical formulation development. Physicochemical properties of both types of polymers provide flexibility of their application. Their precipitation by dense gas as antisolvent provided informative data for subsequent experiment of forming solid dispersions.
Solid dispersions were prepared by precipitation of PVP with several pharmaceutical compounds using dense gas carbon dioxide as antisolvent. We focused on the morphology and particle size control of the products for the first two model drugs, prednisolone and its acetate salt, and then we prepared solid dispersions of a nonsteroidal anti-inflammatory drug, piroxicam. Microcrystals or microspheres were formed where the drug was amorphously dispersed in the polymeric matrix, with drug loadings dependent on initial drug-polymer weight ratios. The existence of interaction between the drug and polymer was confirmed through characterization of their physicochemical properties. The dissolution profiles of solid dispersions showed significant improvement in the dissolution rate of piroxicam compared with their corresponding physical mixtures and plain drug. These results manifest the great potential of this dense gas technique in improving bioavailability of water-insoluble pharmaceutical substances.
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xx, 137 p. : ill.
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Ph.D.
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Includes bibliographical references (p. 94-113)
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Wu
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Ke
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1978-
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Ke Wu
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Li
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Jing
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Jing Li
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Eugene
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Eugene S Hall
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Warmuth
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Ralf
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Ralf Warmuth
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Wang
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Wayne
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Wayne Wang
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Rutgers University
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Graduate School - New Brunswick
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2008
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2008-10
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xx
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Rutgers University Electronic Theses and Dissertations
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Graduate School - New Brunswick Electronic Theses and Dissertations
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doi:10.7282/T39W0FR3
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ETD doctoral
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I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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