Solubilization of Poorly Water-Soluble Drugs: Theory and Applications

Persistent Link:
http://hdl.handle.net/10150/196012
Title:
Solubilization of Poorly Water-Soluble Drugs: Theory and Applications
Author:
He, Yan
Issue Date:
2005
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
This dissertation is based on the theory and applications of the most commonly used solubilization techniques: pH adjustment, cosolvency, micellization, complexation, and the combinations of pH adjustment with one of the other techniques.Chapter 1 provides an overview for the methods which are available to formulate a poorly water-soluble drug based on its administration route.Chapter 2 applies these commonly used techniques to solubilize two structurally related anticancer drugs. The efficiency of each technique is compared for both drugs side by side. It is observed that each technique is more efficient on the drug which has less polarity. However, the achievable final drug concentration in a formulation depends not only on the efficiency of the applied technique, but also on the drug's water solubility.Chapter 3 emphasizes the overall effectiveness of each technique on drugs which have different physicochemical properties. Solubilization profiles for the above techniques are generated for twelve compounds, eight of which are ionizable and studied under both unionized and ionized conditions. This chapter illustrates that the efficiency of the cosolvency, micellization, and complexation on both unionized and ionized drug species can be predicted from their polarities. Thus, the solubility of an ionizable drug can be estimated by using a given solubilizing excipient at any pH to meet the dose requirement.Chapter 4 studies the effect of cosolvent on complex stability. A series of alcohols were used to illustrate the effect of cosolvent size and polarity on the solubilization of a compound. It is proposed that a ternary drug-ligand-cosolvent complex is formed in these combined systemsThis dissertation provides guidance for the selection of a solubilization technique for a compound based on the physicochemical properties and the dose requirement.
Type:
text; Electronic Dissertation
Keywords:
solubilization; formulation; cosolvency; micellization; complexation
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Pharmaceutical Sciences; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Yalkowsky, Samuel H.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleSolubilization of Poorly Water-Soluble Drugs: Theory and Applicationsen_US
dc.creatorHe, Yanen_US
dc.contributor.authorHe, Yanen_US
dc.date.issued2005en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThis dissertation is based on the theory and applications of the most commonly used solubilization techniques: pH adjustment, cosolvency, micellization, complexation, and the combinations of pH adjustment with one of the other techniques.Chapter 1 provides an overview for the methods which are available to formulate a poorly water-soluble drug based on its administration route.Chapter 2 applies these commonly used techniques to solubilize two structurally related anticancer drugs. The efficiency of each technique is compared for both drugs side by side. It is observed that each technique is more efficient on the drug which has less polarity. However, the achievable final drug concentration in a formulation depends not only on the efficiency of the applied technique, but also on the drug's water solubility.Chapter 3 emphasizes the overall effectiveness of each technique on drugs which have different physicochemical properties. Solubilization profiles for the above techniques are generated for twelve compounds, eight of which are ionizable and studied under both unionized and ionized conditions. This chapter illustrates that the efficiency of the cosolvency, micellization, and complexation on both unionized and ionized drug species can be predicted from their polarities. Thus, the solubility of an ionizable drug can be estimated by using a given solubilizing excipient at any pH to meet the dose requirement.Chapter 4 studies the effect of cosolvent on complex stability. A series of alcohols were used to illustrate the effect of cosolvent size and polarity on the solubilization of a compound. It is proposed that a ternary drug-ligand-cosolvent complex is formed in these combined systemsThis dissertation provides guidance for the selection of a solubilization technique for a compound based on the physicochemical properties and the dose requirement.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectsolubilizationen_US
dc.subjectformulationen_US
dc.subjectcosolvencyen_US
dc.subjectmicellizationen_US
dc.subjectcomplexationen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmaceutical Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairYalkowsky, Samuel H.en_US
dc.contributor.committeememberMayersohn, Michaelen_US
dc.contributor.committeememberMyrdal, Paul B.en_US
dc.identifier.proquest1096en_US
dc.identifier.oclc137353957en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.