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Influence of polymers on supersaturation of ibuprofen sodium in vitro and in vivo

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TitleInfo
Title
Influence of polymers on supersaturation of ibuprofen sodium in vitro and in vivo
SubTitle
a mechanistic evaluation
Name (type = personal)
NamePart (type = family)
Terebetski
NamePart (type = given)
Jenna Leschek
NamePart (type = date)
1981-
DisplayForm
Jenna Terebetski
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Michniak-Kohn
NamePart (type = given)
Bozena
DisplayForm
Bozena Michniak-Kohn
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Hatefi
NamePart (type = given)
Arash
DisplayForm
Arash Hatefi
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Minko
NamePart (type = given)
Tamara
DisplayForm
Tamara Minko
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Leung
NamePart (type = given)
Dennis
DisplayForm
Dennis Leung
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2014
DateOther (qualifier = exact); (type = degree)
2014-05
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
To maximize the pharmacological effect of a pain reliever such as ibuprofen, early onset of action is critical. Unfortunately, the acidic nature of ibuprofen minimizes the amount of drug that can be solubilized in the stomach and would be available for immediate absorption upon entry into the intestine. Although the sodium salt of ibuprofen has high aqueous solubility, rapid conversion from the salt to the poorly soluble free acid phase occurs under gastric conditions. In order to prolong the solubility enhancement initially afforded by the salt, the impact of polymers on ibuprofen supersaturation was evaluated in vitro and in vivo, with a focus on establishing a mechanistic understanding for how polymers enabled supersaturation. For this research, dissolution profiles of ibuprofen sodium in the presence of polymers were examined in order to assess degree and duration of supersaturation. In addition, the roles that polymers played in altering drug solubility, pKa, physical form, particle morphology, solution speciation, and media viscosity were probed. Finally in vivo studies were conducted in order to understand the influence of supersaturation on pharmacokinetic parameters. Supersaturation of ibuprofen was effectively prolonged in the presence of a variety of polymers. This was the first example of work that demonstrated prolonged supersaturation when combining a salt form of a drug with a polymeric precipitation inhibitor in the absence of surfactant. Characterization during dissolution demonstrated that mechanism of supersaturation was dependent on specific drug-polymer interactions. In situ formation of stabilized amorphous colloids enabled supersaturation in the presence of PVP-VA64. Intermolecular hydrogen bonding was driving supersaturation in the presence of HPMC by inhibiting nucleation and altering crystal growth. Alternatively, increased media viscosity effectively prolonged supersaturation of ibuprofen when combined with MC. In vitro supersaturation observed with these ibuprofen-polymer formulations translated to an increase in Cmax and an earlier Tmax for the PVP-VA64, MC, and HPC formulations relative to ibuprofen only controls when administered orally to rats. Based on these observations, combining ibuprofen sodium with polymers is a viable formulation approach to prolong supersaturation in the stomach and enable an optimized pharmacokinetic profile in vivo where rapid onset of action is desired.
Subject (authority = RUETD)
Topic
Pharmaceutical Science
Subject (authority = ETD-LCSH)
Topic
Ibuprofen
Subject (authority = ETD-LCSH)
Topic
Absorption (Physiology)
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Identifier
ETD_5356
Identifier (type = doi)
doi:10.7282/T3930RHR
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xxv, 181 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Jenna Leschek Terebetski
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Subject (authority = ETD-LCSH)
Topic
Polymers in medicine
Subject (authority = ETD-LCSH)
Topic
Polymeric drug delivery systems
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Terebetski
GivenName
Jenna
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-03-17 13:44:01
AssociatedEntity
Name
Jenna Terebetski
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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