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Improvement in the bioavailability o...

Yang, Wei.

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Improvement in the bioavailability of poorly water-soluble drugs via pulmonary delivery of nanoparticles.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Improvement in the bioavailability of poorly water-soluble drugs via pulmonary delivery of nanoparticles./
Author:	Yang, Wei.
Description:	258 p.
Notes:	Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: 5459.
Contained By:	Dissertation Abstracts International70-09B.
Subject:	Chemistry, Pharmaceutical. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3372667
ISBN:	9781109366761

Improvement in the bioavailability of poorly water-soluble drugs via pulmonary delivery of nanoparticles.
Yang, Wei.

Improvement in the bioavailability of poorly water-soluble drugs via pulmonary delivery of nanoparticles. - 258 p.

Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: 5459.

Thesis (Ph.D.)--The University of Texas at Austin, 2009.

High throughput screening techniques that are routinely used in modern drug discovery processes result in a higher prevalence of poorly water-soluble drugs. Such drugs often have poor bioavailability issues due to their poor dissolution and/or permeability to achieve sufficient and consistent systemic exposure, resulting in sub-optimal therapeutic efficacies, particularly via oral administration. Alternative formulations and delivery routes are demanded to improve their bioavailability. Nanoparticulate formulations of poorly water-soluble drugs offer improved dissolution profiles. The physiology of the lung makes it an ideal target for non-invasive local and systemic drug delivery for poorly water-soluble drugs.

ISBN: 9781109366761Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Improvement in the bioavailability of poorly water-soluble drugs via pulmonary delivery of nanoparticles.
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020 $a 9781109366761
035 $a (UMI)AAI3372667
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100 1 $a Yang, Wei. $3 1257167
245 1 0 $a Improvement in the bioavailability of poorly water-soluble drugs via pulmonary delivery of nanoparticles.
300 $a 258 p.
500 $a Source: Dissertation Abstracts International, Volume: 70-09, Section: B, page: 5459.
500 $a Advisers: Robert O. Williams, III; Keith P. Johnston.
502 $a Thesis (Ph.D.)--The University of Texas at Austin, 2009.
520 $a High throughput screening techniques that are routinely used in modern drug discovery processes result in a higher prevalence of poorly water-soluble drugs. Such drugs often have poor bioavailability issues due to their poor dissolution and/or permeability to achieve sufficient and consistent systemic exposure, resulting in sub-optimal therapeutic efficacies, particularly via oral administration. Alternative formulations and delivery routes are demanded to improve their bioavailability. Nanoparticulate formulations of poorly water-soluble drugs offer improved dissolution profiles. The physiology of the lung makes it an ideal target for non-invasive local and systemic drug delivery for poorly water-soluble drugs.
520 $a In Chapter 2, a particle engineering process ultra-rapid freezing (URF) was utilized to produce nanostructured aggregates of itraconazole (ITZ), a BCS class II drug, for pulmonary delivery with approved biocompatible excipients. The obtained formulation, ITZ:mannitol:lecithin (1:0.5:0.2, w/w), i.e. URF-ITZ, was a solid solution with high surface area and ability to achieve high magnitude of supersaturation. An aqueous colloidal dispersion of URF-ITZ was suitable for nebulization, which demonstrated optimal aerodynamic properties for deep lung delivery and high lung and systemic ITZ levels when inhaled by mice.
520 $a The significantly improved systemic bioavailability of inhaled URF-ITZ was mainly ascribed to the amorphous morphology that raised the drug solubility. The effect of supersaturation of amorphous URF-ITZ relative to nanocrystalline ITZ on bioavailability following inhalation was evaluated in Chapter 3. The nanoparticulate amorphous ITZ composition resulted in a significantly higher systemic bioavailability than for the nanocrystalline ITZ composition, as a result of the higher supersaturation that increased the permeation.
520 $a In Chapter 4, pharmacokinetics of inhaled nebulized aerosols of solubilized ITZ in solution versus nanoparticulate URF-ITZ colloidal dispersion were investigated, under the hypothesis that solubilized ITZ can be absorbed faster through mucosal membrane than the nanoparticulate ITZ. Despite similar ITZ lung deposition, the inhaled solubilized ITZ demonstrated significantly faster systemic absorption across lung epithelium relative to nanoparticulate ITZ in mice, due in part to the elimination of the phase-to-phase transition of nanoparticulate ITZ.
590 $a School code: 0227.
650 4 $a Chemistry, Pharmaceutical. $3 550957
650 4 $a Engineering, Chemical. $3 1018531
650 4 $a Health Sciences, Pharmacy. $3 1017737
690 $a 0491
690 $a 0542
690 $a 0572
710 2 $a The University of Texas at Austin. $b Pharmacy. $3 1021716
773 0 $t Dissertation Abstracts International $g 70-09B.
790 1 0 $a Williams, Robert O., III, $e advisor
790 1 0 $a Johnston, Keith P., $e advisor
790 1 0 $a McGinity, James W. $e committee member
790 1 0 $a McConville, Jason T. $e committee member
790 1 0 $a Wiederhold, Nathan P. $e committee member
790 $a 0227
791 $a Ph.D.
792 $a 2009
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3372667