Persistent Link:
http://hdl.handle.net/10150/193915
Title:
Estimation of Ethanol/Water Solubility Profiles
Author:
Machatha, Stephen Gitu
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 goal of this study was to develop a simple means of estimating the cosolvent/water solubility profile using just the available properties (logKow, dielectric constant etc.) of the solute, cosolvent and water. Ethanol was used as the model cosolvent.One of the most commonly used polarity indicators is the octanol/water partition coefficient (logKow). Numerous programs are used to predict the logKow. The calculated values of logKow from three of the most commonly used programs ClogP®, ACD/logPdb® and KowWin® were compared to experimental values. It was found that all three programs have a user friendly interface but ClogP appears to be more accurate.While the ethanol/water solubility profiles of very polar and very non-polar drugs are monotonic, many semi-polar drugs show a maximum solubility at an ethanol volume fraction (fmax) between zero and one. A new empirical function that describes this deviation from linearity was applied to the experimental data forfifty-one compounds. The proposed model was a more accurate predictor of the co-solvent solubility profile than a general third order polynomial with the samenumber of parameters. The fmax value was also accurately predicted from the first derivative of the model.A sigmoidal relationship was observed between the value of fmax and logKow of the solute. Combining this sigmoidal relationship with the previously reportedlinear relationship between logKow and the initial slope of the plot of log solubility vs. ethanol composition enables the estimation of the totalethanol/water solubility profiles of semi-polar compounds from just logKow.A new bilinear function was also introduced to address the deviation from linearity. This model accounts for both the initial and terminal slopes in theethanol/water solubility profiles of semi-polar solutes. The proposed model is dependent only on logKow and an empirical constant that is cosolvent specific. It is also more accurate than the log-linear model and a general parabolic model.A solubility case study using Antalarmin, a novel stress inhibitor was performed.This study illustrates the use of cosolvents as solubility enhancers as well as pH,surfactants, complexants and lipid based systems.
Type:
text; Electronic Dissertation
Keywords:
Solubility; Ethanol; Stability; LogP
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.titleEstimation of Ethanol/Water Solubility Profilesen_US
dc.creatorMachatha, Stephen Gituen_US
dc.contributor.authorMachatha, Stephen Gituen_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 goal of this study was to develop a simple means of estimating the cosolvent/water solubility profile using just the available properties (logKow, dielectric constant etc.) of the solute, cosolvent and water. Ethanol was used as the model cosolvent.One of the most commonly used polarity indicators is the octanol/water partition coefficient (logKow). Numerous programs are used to predict the logKow. The calculated values of logKow from three of the most commonly used programs ClogP®, ACD/logPdb® and KowWin® were compared to experimental values. It was found that all three programs have a user friendly interface but ClogP appears to be more accurate.While the ethanol/water solubility profiles of very polar and very non-polar drugs are monotonic, many semi-polar drugs show a maximum solubility at an ethanol volume fraction (fmax) between zero and one. A new empirical function that describes this deviation from linearity was applied to the experimental data forfifty-one compounds. The proposed model was a more accurate predictor of the co-solvent solubility profile than a general third order polynomial with the samenumber of parameters. The fmax value was also accurately predicted from the first derivative of the model.A sigmoidal relationship was observed between the value of fmax and logKow of the solute. Combining this sigmoidal relationship with the previously reportedlinear relationship between logKow and the initial slope of the plot of log solubility vs. ethanol composition enables the estimation of the totalethanol/water solubility profiles of semi-polar compounds from just logKow.A new bilinear function was also introduced to address the deviation from linearity. This model accounts for both the initial and terminal slopes in theethanol/water solubility profiles of semi-polar solutes. The proposed model is dependent only on logKow and an empirical constant that is cosolvent specific. It is also more accurate than the log-linear model and a general parabolic model.A solubility case study using Antalarmin, a novel stress inhibitor was performed.This study illustrates the use of cosolvents as solubility enhancers as well as pH,surfactants, complexants and lipid based systems.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectSolubilityen_US
dc.subjectEthanolen_US
dc.subjectStabilityen_US
dc.subjectLogPen_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, Paulen_US
dc.identifier.proquest1659en_US
dc.identifier.oclc137356643en_US
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