Dissertation
Physiological based models of drug delivery via nasal and oral cavity
Doctor of Philosophy (Ph.D.), Drexel University
Sep 2017
DOI:
https://doi.org/10.17918/etd-7865
Abstract
The purpose of this work is to build physiological based models for simulating intra oral and intra nasal drug absorption, distribution and elimination. Rat and human physiological parameters, drug physicochemical properties and tissue concentration time data were all obtained from published literature. Paracetamol and a neuroactive peptide were used as model drugs to test the model predictions. Gastroplus v9.5, and Matlab Simbiology software were used to mathematically integrate the systems with drug specific data and run the simulations. The intra oral model showed good prediction of observed pharmacokinetic profiles for paracetamol. The model predicted about 12% of the dose were absorbed through the oral mucosa and ~82% absorbed in the small intestine. This is quite significant because it showed that delivery of paracetamol through the intra oral route is feasible. The model developed provided a cost-effective tool for simulating the effect of different intra oral formulations on the exposure to paracetamol in human prior to in vivo studies. The model also highlighted the disconnect between the observed plasma concentration and pharmacodynamic effect, suggested a potential of additional transport mechanism from the oral mucosa to the paracetamol effect site in the spinal cord. The intra nasal model showed good prediction of the observed blood and brain pharmacokinetic profile of neuroactive peptide following rapid uptake from the rat nasal mucosa. The model provided a conceptual framework for modeling and simulating the absorption, distribution and elimination of model drug through olfactory, trigeminal and systemic pathways. The model suggested the rapid raise of drug concentration in the brain tissue
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Details
- Title
- Physiological based models of drug delivery via nasal and oral cavity
- Creators
- Thuy Thanh Tran - DU
- Contributors
- Joseph Edward Bentz (Advisor) - Drexel University (1970-)Valeriu Damian (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- 59 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 7865; 991014632073004721