RUcore: Rutgers University Community Repository
Solubility and activity coefficient of pharmaceutical compounds in liquid organic solvents
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
Solubility and activity coefficient of pharmaceutical compounds in liquid organic solvents
SubTitle
PartName
PartNumber
NonSort
Identifier
(displayLabel = );
(invalid = )
ETD_2092
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000051883
Language
(objectPart = )
LanguageTerm
(authority = ISO639-2);
(type = code)
eng
Genre
(authority = marcgt)
theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Chemical and Biochemical Engineering
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
Solvents
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Pharmaceutical chemistry
Abstract
The production of pharmaceuticals and oligo-sized biochemicals involves liquid solvent selection as a function of solubility, for purification, chemical reaction and formulation. Selecting the optimum solvent for a particular application is of critical importance to developing efficient process; choosing solvents for pharmaceutical processes has been based on experience and empirical description of experimental results. Therefore, rapid and reliable prediction of drug solubility is needed for design and optimization of cost-effective manufacturing processes.
A semi-automated, two-millimeter-scale method, was designed and validated for rapid measurement of equilibrium solubility of crystalline solids in liquid solvents. Solubilities and stability of model compounds such as lovastatin, simvastatin, and artemisinin, were measured in several solvents and exhibited a maximum deviation of 5% compared to literature data. Extrapolation of the solubility in the form of activity coefficient was determined to agree with the experimental data.
Calculation of the ideal solubility of crystalline solid in liquid solvent requires knowledge of the difference in molar heat capacity of the solid and super-cooled liquid solute at the solution temperature. This is a hypothetical parameter and therefore, can not be measured directly, and hence, three assumptions are commonly used in the literature for its estimation. Evaluation of the assumptions revealed some thermodynamic inconsistencies. A new strategy was explored to estimate the difference in molar heat capacity, allowing the experimental solubility data to be fitted to the Two-Liquid-Non-Random (NRTL) activity coefficient equation to obtain the model binary energetic interaction parameters. The binary interaction parameters were successfully used to estimate solubility of the model compounds in mixed solvents.
In free energy perturbation (FEP) methods, mutation of lovastatin to simvastatin in five different solvents were carried out to obtain the free energy differences, and hence the ratio of the activity coefficients at infinite dilution. The FEP calculation reproduced the experimental solubility results quite well, and provides a basis for development of molecular modeling for estimation of pharmaceutical compounds in liquid solvents.
A semi-automated, two-millimeter-scale method, was designed and validated for rapid measurement of equilibrium solubility of crystalline solids in liquid solvents. Solubilities and stability of model compounds such as lovastatin, simvastatin, and artemisinin, were measured in several solvents and exhibited a maximum deviation of 5% compared to literature data. Extrapolation of the solubility in the form of activity coefficient was determined to agree with the experimental data.
Calculation of the ideal solubility of crystalline solid in liquid solvent requires knowledge of the difference in molar heat capacity of the solid and super-cooled liquid solute at the solution temperature. This is a hypothetical parameter and therefore, can not be measured directly, and hence, three assumptions are commonly used in the literature for its estimation. Evaluation of the assumptions revealed some thermodynamic inconsistencies. A new strategy was explored to estimate the difference in molar heat capacity, allowing the experimental solubility data to be fitted to the Two-Liquid-Non-Random (NRTL) activity coefficient equation to obtain the model binary energetic interaction parameters. The binary interaction parameters were successfully used to estimate solubility of the model compounds in mixed solvents.
In free energy perturbation (FEP) methods, mutation of lovastatin to simvastatin in five different solvents were carried out to obtain the free energy differences, and hence the ratio of the activity coefficients at infinite dilution. The FEP calculation reproduced the experimental solubility results quite well, and provides a basis for development of molecular modeling for estimation of pharmaceutical compounds in liquid solvents.
PhysicalDescription
Form
(authority = gmd)
electronic resource
Extent
xii, 148 p. : ill.
InternetMediaType
application/pdf
InternetMediaType
text/xml
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references (p. 134-141)
Note
(type = statement of responsibility)
by Joseph Nti-Gyabaah
Name
(ID = NAME-1);
(type = personal)
NamePart
(type = family)
Nti-Gyabaah
NamePart
(type = given)
Joseph
Role
RoleTerm
(authority = RULIB);
(type = )
author
DisplayForm
Joseph Nti-Gyabaah
Name
(ID = NAME-2);
(type = personal)
NamePart
(type = family)
Chiew
NamePart
(type = given)
Yee
Role
RoleTerm
(authority = RULIB);
(type = )
chair
Affiliation
Advisory Committee
DisplayForm
Yee Clement Chiew
Name
(ID = NAME-3);
(type = personal)
NamePart
(type = family)
Pedersen
NamePart
(type = given)
Henrik
Role
RoleTerm
(authority = RULIB);
(type = )
internal member
Affiliation
Advisory Committee
DisplayForm
Henrik Pedersen
Name
(ID = NAME-4);
(type = personal)
NamePart
(type = family)
Shapley
NamePart
(type = given)
Nina
Role
RoleTerm
(authority = RULIB);
(type = )
internal member
Affiliation
Advisory Committee
DisplayForm
Nina Shapley
Name
(ID = NAME-5);
(type = personal)
NamePart
(type = family)
Simon
NamePart
(type = given)
James
Role
RoleTerm
(authority = RULIB);
(type = )
internal member
Affiliation
Advisory Committee
DisplayForm
James Simon
Name
(ID = NAME-6);
(type = personal)
NamePart
(type = family)
Linden
NamePart
(type = given)
Thomas
Role
RoleTerm
(authority = RULIB);
(type = )
outside member
Affiliation
Advisory Committee
DisplayForm
Thomas Linden
Name
(ID = NAME-1);
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB);
(type = )
degree grantor
Name
(ID = NAME-2);
(type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm
(authority = RULIB);
(type = )
school
OriginInfo
DateCreated
(point = );
(qualifier = exact)
2009
DateOther
(qualifier = exact);
(type = degree)
2009-10
Place
PlaceTerm
(type = code)
xx
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
Location
PhysicalLocation
(authority = marcorg);
(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3D21XSC
Genre
(authority = ExL-Esploro)
ETD doctoral
Back to the top
Rights
RightsDeclaration
(AUTHORITY = GS);
(ID = rulibRdec0006)
The author owns the copyright to this work
Copyright
Status
Copyright protected
Notice
Note
Availability
Status
Open
Reason
Permission or license
Note
RightsHolder
(ID = PRH-1);
(type = personal)
Name
FamilyName
Nti-Gyabaah
GivenName
Joseph
Role
Copyright holder
RightsEvent
(ID = RE-1);
(AUTHORITY = rulib)
Type
Permission or license
Label
Place
DateTime
Detail
AssociatedEntity
(ID = AE-1);
(AUTHORITY = rulib)
Role
Copyright holder
Name
Joseph Nti-Gyabaah
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
(ID = AO-1);
(AUTHORITY = rulib)
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.
Back to the top
Technical
ContentModel
ETD
MimeType
(TYPE = file)
application/pdf
MimeType
(TYPE = container)
application/x-tar
FileSize
(UNIT = bytes)
1576960
Checksum
(METHOD = SHA1)
a5be3978f51288595ac3cebf9ff1a9b4dea65e9c
Back to the top
Statistical Profile