Drug Solubilization using N-Methyl Pyrrolidone: Efficiency and Mechanism

Persistent Link:
http://hdl.handle.net/10150/194616
Title:
Drug Solubilization using N-Methyl Pyrrolidone: Efficiency and Mechanism
Author:
Sanghvi, Ritesh
Issue Date:
2006
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:
The solubilization efficiency of N-methyl pyrrolidone (NMP) has been determined and compared to that of ethanol and propylene glycol for 13 poorly soluble drugs. NMP is a more efficient solubilizer for all these drugs. The solubility enhancement as high as about 800-fold is obtained in 20% v/v NMP solution as compared to water. The mechanism of drug solubilization by NMP has also been investigated. It is proposed that NMP enhances drug solubility by simultaneously acting as a cosolvent and a complexing agent. A mathematical model to estimate drug solubility in NMP-water mixture is proposed, according to which the total solubility enhancement is a sum of these two effects. This model describes the experimental data well and is more accurate than the existing models. The cosolvent effect of NMP is demonstrated by a large and uniform reduction in the surface tension of water as a function of its concentration. Complexation is supported by the fact that it's strength is reduced upon increasing the temperature or lowering the polarity of the medium. Increasing the medium polarity on the other hand strengthens complexation. A strong correlation exists between log Kow of the drugs and the respective cosolvency coefficients. The correlation between log Kow and the respective complexation coefficients is weak suggesting that factors like molecular shape and aromaticity are significant in determining the complexation strength. This is confirmed by the absence of a significant complexation with linear molecules. It is also noticed that besides NMP, two other pyrrolidone derivatives enhance drug solubility following the same mechanism.
Type:
text; Electronic Dissertation
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Pharmaceutical Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Yalkowsky, Samuel H.
Committee Chair:
Yalkowsky, Samuel H.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleDrug Solubilization using N-Methyl Pyrrolidone: Efficiency and Mechanismen_US
dc.creatorSanghvi, Riteshen_US
dc.contributor.authorSanghvi, Riteshen_US
dc.date.issued2006en_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.abstractThe solubilization efficiency of N-methyl pyrrolidone (NMP) has been determined and compared to that of ethanol and propylene glycol for 13 poorly soluble drugs. NMP is a more efficient solubilizer for all these drugs. The solubility enhancement as high as about 800-fold is obtained in 20% v/v NMP solution as compared to water. The mechanism of drug solubilization by NMP has also been investigated. It is proposed that NMP enhances drug solubility by simultaneously acting as a cosolvent and a complexing agent. A mathematical model to estimate drug solubility in NMP-water mixture is proposed, according to which the total solubility enhancement is a sum of these two effects. This model describes the experimental data well and is more accurate than the existing models. The cosolvent effect of NMP is demonstrated by a large and uniform reduction in the surface tension of water as a function of its concentration. Complexation is supported by the fact that it's strength is reduced upon increasing the temperature or lowering the polarity of the medium. Increasing the medium polarity on the other hand strengthens complexation. A strong correlation exists between log Kow of the drugs and the respective cosolvency coefficients. The correlation between log Kow and the respective complexation coefficients is weak suggesting that factors like molecular shape and aromaticity are significant in determining the complexation strength. This is confirmed by the absence of a significant complexation with linear molecules. It is also noticed that besides NMP, two other pyrrolidone derivatives enhance drug solubility following the same mechanism.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_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.advisorYalkowsky, Samuel H.en_US
dc.contributor.chairYalkowsky, Samuel H.en_US
dc.contributor.committeememberMayersohn, Michaelen_US
dc.contributor.committeememberMyrdal, Paulen_US
dc.contributor.committeememberWirth, Mary J.en_US
dc.identifier.proquest1966en_US
dc.identifier.oclc659746543en_US
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