Persistent Link:
http://hdl.handle.net/10150/196098
Title:
An Investigation of Solute Solubility in the Propellant HFA-134a
Author:
Hoye, Julie Annalisa
Issue Date:
2007
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 reformulation of pressurized metered dose inhalers (MDIs) with hydrofluoroalkanes (HFAs) from chlorofluorocarbons (CFCs) has given rise to many solubility challenges. Compounds and excipients previously used in CFCs were observed to have significantly different solubility values in HFA-134a. In this investigation, the solubility values of solid organic solutes were determined in pure HFA-134a and HFA-134a with cosolvent (0 - 20% w/w ethanol). The solubilities of solid solutes in HFA-134a were also compared with those in 2H,3H-decafluoropentane (DFP) in order to assess the suitability of DFP as a liquid model propellant. The experimental set of solutes display diverse physico-chemical properties and yielded solubility values that ranged over four orders of magnitude. The experimental solubilities were compared to calculated values obtained from ideal solubility and regular solution theory models. While the theoretical models did not offer absolute solubility estimations, a clear correlation with the ideal solubility (melting point) was noted. Further consideration utilizing multiple linear regression models afforded correlations based on molecular properties. Regression models, containing melting point and logP (or molar volume) resulted in promising correlations in both pure HFA-134a and HFA-134a/cosolvent systems where the average absolute errors ranged from 0.49 to 0.82 log units, (average factor errors of 3.09 and 6.61, respectively). In general, a linear relationship was observed between log mole fraction solubility in HFA-134a and fraction ethanol. The effect on solubilization ranged from 1.3 to 99.4 times when 20% w/w ethanol was introduced, relative to pure HFA-134a. DFP appears to be a promising liquid model for pure HFA-134a for pre-formulation calculations. A two parameter equation were found to be significant in pure HFA-134a where the average absolute error (AAE) value was 0.61 log units (average factor errors of 4.07).
Type:
text; Electronic Dissertation
Keywords:
structure-property relationship; solubility; physicochemical properties; HFA-134a
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Pharmaceutical Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Myrdal, Paul B.
Committee Chair:
Myrdal, Paul B.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleAn Investigation of Solute Solubility in the Propellant HFA-134aen_US
dc.creatorHoye, Julie Annalisaen_US
dc.contributor.authorHoye, Julie Annalisaen_US
dc.date.issued2007en_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 reformulation of pressurized metered dose inhalers (MDIs) with hydrofluoroalkanes (HFAs) from chlorofluorocarbons (CFCs) has given rise to many solubility challenges. Compounds and excipients previously used in CFCs were observed to have significantly different solubility values in HFA-134a. In this investigation, the solubility values of solid organic solutes were determined in pure HFA-134a and HFA-134a with cosolvent (0 - 20% w/w ethanol). The solubilities of solid solutes in HFA-134a were also compared with those in 2H,3H-decafluoropentane (DFP) in order to assess the suitability of DFP as a liquid model propellant. The experimental set of solutes display diverse physico-chemical properties and yielded solubility values that ranged over four orders of magnitude. The experimental solubilities were compared to calculated values obtained from ideal solubility and regular solution theory models. While the theoretical models did not offer absolute solubility estimations, a clear correlation with the ideal solubility (melting point) was noted. Further consideration utilizing multiple linear regression models afforded correlations based on molecular properties. Regression models, containing melting point and logP (or molar volume) resulted in promising correlations in both pure HFA-134a and HFA-134a/cosolvent systems where the average absolute errors ranged from 0.49 to 0.82 log units, (average factor errors of 3.09 and 6.61, respectively). In general, a linear relationship was observed between log mole fraction solubility in HFA-134a and fraction ethanol. The effect on solubilization ranged from 1.3 to 99.4 times when 20% w/w ethanol was introduced, relative to pure HFA-134a. DFP appears to be a promising liquid model for pure HFA-134a for pre-formulation calculations. A two parameter equation were found to be significant in pure HFA-134a where the average absolute error (AAE) value was 0.61 log units (average factor errors of 4.07).en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectstructure-property relationshipen_US
dc.subjectsolubilityen_US
dc.subjectphysicochemical propertiesen_US
dc.subjectHFA-134aen_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.advisorMyrdal, Paul B.en_US
dc.contributor.chairMyrdal, Paul B.en_US
dc.contributor.committeememberMyrdal, Paul B.en_US
dc.contributor.committeememberYalkowsky, Samuelen_US
dc.contributor.committeememberMayersohn, Michaelen_US
dc.identifier.proquest2300en_US
dc.identifier.oclc659748151en_US
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