Administering 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.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/312666 |
| Date | January 2013 |
| Creators | Evans, Daniel Christopher |
| Contributors | Yalkowsky, Samuel H., Yalkowsky, Samuel H., Mayersohn, Michael, Myrdal, Paul B., Curry, Joan E., Schaap, Marcel G. |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | en_US |
| Detected Language | English |
| Type | text, Electronic Dissertation |
| 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. |
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