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dc.contributor.advisorBurton, Philip S.
dc.contributor.authorYancon, Andrea Rose
dc.description32 p.en_US
dc.description.abstractA prototype artificial stomach and duodenum (ASD) model has been developed for in vitro testing of drug compounds in biopharmaceutical research that simulates the dynamic pH conditions, bile salt concentrations, temperature, and gastric motility conditions of the in vivo environment. Cinnarizine and Dipyridamole are two weakly basic drug compounds with low intrinsic solubility, showing a higher solubility in the acidic conditions of the stomach and a lower solubility in the more neutral conditions of the duodenum. Solubility profiles at varying pH values of the two compounds in thermodynamically stable conditions predict the precipitation and therefore unavailability for absorption and use by the body of the compounds upon entering the small intestine, however,they are observed in vivo to be absorbed and biologically available. These observations suggest greater solubility in the intestine than predictable from idealized in vitroconsiderations. This experiment examines the ability of the dynamic nature of the ASD to examine a supersaturation phenomenon that the current trend of using static state solubility profiling fails to predict. Simulated gastric fluid (SGF) was used in the ASD as well as simulated intestinal fluids, both simple (SIF) and more complex with bile salts (FaSSIF). Solubility profiles for each compound were created and compared to the solubility values seen with ASD use. In the ASD model, concentrations of the compounds were achievedthat exceeded the maximum solubility predicted by the solubility profile, implying supersaturation. This demonstrates an advantage of using a dynamic system such as theASD for makingin vitro / in vivo correlations. The use of the more complex intestinal fluid (FaSSIF) created a weaker buffer system in the duodenum,preventing the duodenum pH from rising back to its initial value. This caused some difficulty in utilizing such a solution in this ASD model. However, the emulsifyingpowerofthe solution was seen as Dipyridamole exhibited a much higher solubility in FaSSIF than in SIF. The reproducibility of the instrument was examined, showing increased reproducibility between replicates after the tubing had recently been both changed and broken in. The ASD has a future in predicting in vivo solubility behavior of new drug candidates in a drug discovery setting when the inherent variation in the tubing and pumps is understood and the analysis is confined to the most robust trends.en_US
dc.description.sponsorshipADMETRx, Kalamazoo, Michigan
dc.publisherKalamazoo Collegeen_US
dc.relation.ispartofKalamazoo College Chemistry Senior Individualized Projects Collection
dc.rightsU.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder. All rights reserved.
dc.titleThe Characterization of an Artificial Stomach and Duodenum System (ASD) to Predict in Vivoperformance of Drugs: Examining the Behavior of the Poorly Soluble Weak Bases Cinnarizine and Dipyridamoleen_US

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  • Chemistry Senior Individualized Projects [827]
    This collection includes Senior Individualized Projects (SIP's) completed in the Chemistry Department. Abstracts are generally available to the public, but PDF files are available only to current Kalamazoo College students, faculty, and staff.

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