Show simple item record

dc.contributor.advisorYalkowsky, Samuel H.en_US
dc.contributor.authorEvans, Daniel Christopher
dc.creatorEvans, Daniel Christopheren_US
dc.date.accessioned2014-02-12T00:01:20Z
dc.date.available2014-02-12T00:01:20Z
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/10150/312666
dc.description.abstractAdministering drug therapy through the intravenous route ensures rapid, and complete, bioavailability, which can be critical in an emergency situation. However, bypassing all of its protective barriers leaves the body vulnerable to harm if the parenteral formulation becomes unstable when mixed with the blood. An example of this formulation instability is the precipitation of poorly water-soluble drugs after mixing with the blood's aqueous environment. This happens when parenteral formulations rely too heavily upon the solution pH, and excipients, to increase the drug solubility. This precipitation in the blood can damage venous cell membranes producing symptoms ranging from mild skin irritation to death. To screen potential drug formulations for problems such as injection site drug precipitation, pharmaceutical companies have traditionally used costly and time consuming animal studies. To reduce the amount of pre-clinical animal studies necessary to find an optimal IV formulation, an in vitro device to detect injection site drug precipitation is introduced. In addition to the device, software that simulates the dilution of a parenteral drug formulation with blood upon administration has been developed and is introduced. Both the device and software were tested on commercially available formulations plus one formulation currently in clinical trials. The results and capabilities of the new device were compared to those obtained using an earlier in vitro device. Finally, a robust model for early screening of injection site precipitation is developed using both the in vitro device and software.
dc.language.isoen_USen
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.subjectin vitroen_US
dc.subjectparenteralen_US
dc.subjectphlebitisen_US
dc.subjectprecipitationen_US
dc.subjectsolubilityen_US
dc.subjectPharmaceutical Sciencesen_US
dc.subjectDrugen_US
dc.titlePredicting Injection Site Drug Precipitationen_US
dc.typetexten
dc.typeElectronic Dissertationen
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.contributor.committeememberYalkowsky, Samuel H.en_US
dc.contributor.committeememberMayersohn, Michaelen_US
dc.contributor.committeememberMyrdal, Paul B.en_US
dc.contributor.committeememberCurry, Joan E.en_US
dc.contributor.committeememberSchaap, Marcel G.en_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmaceutical Sciencesen_US
thesis.degree.namePh.D.en_US
refterms.dateFOA2018-08-30T17:17:31Z
html.description.abstractAdministering drug therapy through the intravenous route ensures rapid, and complete, bioavailability, which can be critical in an emergency situation. However, bypassing all of its protective barriers leaves the body vulnerable to harm if the parenteral formulation becomes unstable when mixed with the blood. An example of this formulation instability is the precipitation of poorly water-soluble drugs after mixing with the blood's aqueous environment. This happens when parenteral formulations rely too heavily upon the solution pH, and excipients, to increase the drug solubility. This precipitation in the blood can damage venous cell membranes producing symptoms ranging from mild skin irritation to death. To screen potential drug formulations for problems such as injection site drug precipitation, pharmaceutical companies have traditionally used costly and time consuming animal studies. To reduce the amount of pre-clinical animal studies necessary to find an optimal IV formulation, an in vitro device to detect injection site drug precipitation is introduced. In addition to the device, software that simulates the dilution of a parenteral drug formulation with blood upon administration has been developed and is introduced. Both the device and software were tested on commercially available formulations plus one formulation currently in clinical trials. The results and capabilities of the new device were compared to those obtained using an earlier in vitro device. Finally, a robust model for early screening of injection site precipitation is developed using both the in vitro device and software.


Files in this item

Thumbnail
Name:
azu_etd_13171_sip1_m.pdf
Size:
2.570Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record