Dissertation
Quantitative analysis of molecular processes by single molecule spectroscopy and development of analytical methods to study drug dissolution
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Spring 2021
DOI: 10.17077/etd.005798
Abstract
This research work includes studies in two different scopes in analytical chemistry. The first direction presents fundamental studies involved with single molecule measurements with a confocal microscope. A central concept in confocal microscopy, the point spread function was explored with theoretical simulations to depict its impact on the experimental measurements of molecular diffusion at single molecule regime. In measurements using a confocal microscope, multiple layers with different refractive indices exist in the observation medium, causing alterations in the point spread function. Understanding the effect of altered point spread function on the obtained diffusion information is essential to produce robust measurements. Besides the study of point spread function, the heterogeneity of molecular processes in nanoporous materials was studied with single molecule spectroscopy. Nanoporous materials are utilized in a broad spectrum of applications across chemical separations, catalysis, drug delivery, biosensing, and environmental remediation. To improve the efficacy of the applications, having a comprehensive understanding of the molecular processes in the confined media of nanopores is essential. Heterogeneity in physicochemical properties of the nanoporous materials results in the formation of a heterogeneous environment for varying molecular processes to occur in the nanopores. The ensemble average measurements have limited capability to observe heterogeneity. Single molecule spectroscopy has been developed as an effective tool to reveal hidden subpopulations that are covered under a merged larger population in ensemble measurements, providing a comprehensive understanding of the molecular processes that control the functional applications of the nanoporous materials. In this research work, heterogeneity in the molecular processes in nanopores was examined by analyzing photon emission from single fluorescent molecules undergoing diffusion and adsorption inside silica nanopores.
The second research direction involved in this work is developing methods for analyzing dissolution of solid drug tablets. The pharmaceutical industry has become the largest sector for the employment of chemists. Dissolution is a key analytical test for drugs in solid oral dosage forms. However, dissolution-related topics are not well taught in undergraduate education to help students in chemistry major to be prepared for their future career. To address this lack of training in both hands-on experience and analysis of dissolution testing in undergraduate teaching laboratories, a dissolution protocol was established for undergraduate education. The protocol was first developed in a research laboratory setting, and then performed by students in multiple sessions across various semesters. The protocol was proven to be reproducible by analyzing student results and comparing the results to the criteria mandated by the Food and Drug Administration (FDA). Further exploration of analyzing dissolution kinetics with a novel approach utilizing two-dimensional correlation spectroscopy was conducted. This approach was evaluated and compared with the existing FDA-regulated methods, showing advantages and potential in effectively discerning dissolution kinetic profiles.
Details
- Title: Subtitle
- Quantitative analysis of molecular processes by single molecule spectroscopy and development of analytical methods to study drug dissolution
- Creators
- Chengxuan Guo
- Contributors
- M Lei Geng (Advisor)Gary W Small (Advisor)Renée S Cole (Committee Member)Leonard R MacGillivray (Committee Member)Alexei V Tivanski (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Chemistry
- Date degree season
- Spring 2021
- DOI
- 10.17077/etd.005798
- Publisher
- University of Iowa
- Number of pages
- xviii, 170 pages
- Copyright
- Copyright 2021 Chengxuan Guo
- Language
- English
- Description illustrations
- illustrations (some color)
- Description bibliographic
- Includes bibliographical references (pages 153-170)
- Public Abstract (ETD)
Nanoporous materials are utilized in a broad spectrum of applications in chemical separations, drug delivery, environmental remediation, biosensing, and catalytic reactions. How molecules transport in nanopores is critical to the applications involving nanoporous materials. Single molecule spectroscopy is an effective tool to study the details of molecular processes occurring in the nanopores. We performed an analysis of molecular processes with single molecule spectroscopy based on confocal microscopy. By conducting experiments and theoretical simulations, we explored some fundamental questions: the effect on single molecule detection by alteration of the point spread function, the existence of multiple populations in molecular events in nanopores.
Besides the research on single molecule spectroscopy, we developed analytical methods to study drug dissolution, a key test in the pharmaceutical field. An experimental protocol for drug dissolution testing was developed and added to the undergraduate laboratory curriculum. This protocol benefits undergraduate students by helping them gain technical experience in the pharmaceutical industry. Besides the experimental protocol for educational purposes, we explored the comparison of dissolution profiles with the approach of two-dimensional correlation spectroscopy, which shows promising advantages compared to currently established methods regulated by the Food and Drug Administration.
- Academic Unit
- Chemistry
- Record Identifier
- 9984097366502771
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