Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Biomedical Engineering

Supervisor

Mequanint, Kibret

Abstract

Controlled-release tablets enhance the effectiveness of therapies for various clinical conditions. Photocrosslinkable polyanhydrides that undergo surface erosion were recently introduced as suitable materials for manufacturing tablets with tunable release profiles. However, their erosion behavior has not been comprehensively studied. In this thesis, the erosion kinetics of photocrosslinkable polyanhydrides was studied by exploring the impact of different parameters (the polymer composition and geometry, as well as the temperature, pH, and shaking rate of the solution during the in vitro experiments) on their mass loss profiles, followed by a release kinetic model fitting. The results indicate that the temperature was the only parameter that could affect the induction period (the lag time) substantially. Moreover, polymers with the same surface area to volume ratios showed similar mass loss percentage despite their dissimilar volumes and surface areas. Although tablets with adjustable release profiles have been studied before, lack of a fast and large-scale production technique is a significant limitation that holds back their widespread application. A high-throughput fabrication platform was developed that was then utilized to manufacture controlled-release polyanhydride tablets. Tunable release profiles with the high-throughput fabricated tablets were achieved.

Summary for Lay Audience

Oral drug delivery is the preferred route for medication administration due to its lower cost and higher convenience for patients compared to other methods such as injection and implantation. The conventional form of oral tablets, however, requires multiple administrations to maintain the concentration of drugs in the bloodstream at an effective level. Controlled-release tablets have emerged as an alternative that can sustain the drug dosage at an effective level for a long period of time, aiming at enhancing the effectiveness of therapies in various clinical conditions. In addition, tablets with adjustable release profiles of the drug have been explored to improve the treatment efficacy for diseases that require different temporal profiles of the drug concentration. These tablets are typically made of a special class of polymers called biodegradable polymers, meaning that they are safely decomposed by the human body after they release the drug.

Polyanhydride is a biodegradable polymer that is considered as an appropriate option for being used in the fabrication of tablets with adjustable release profiles. Polyanhydrides are mostly eroded from their surfaces at predictable rates when they are exposed to the aqueous media. Understanding the erosion behavior (and hence the mass loss profile) of a newly introduced type of polyanhydride is an essential step before its utilization in fabricating tablets with adjustable release profiles. In this thesis, we first studied the erosion behavior of the new type of polyanhydride by exploring the impact of different parameters on their mass loss profiles. Moreover, we fitted the experimental mass loss data to different release kinetic models to gain a better understanding of the erosion behavior.

Although tablets with adjustable release profiles have been around for a while, lack of a fast and large-scale production technique has remained an important limitation that holds back their widespread application. We developed a high-throughput fabrication platform that we then utilized to manufacture polyanhydride tablets with controllable release profiles. We achieved tunable release profiles with the high-throughput fabricated tablets. Finally, we increased the capacity of the tablets for drug loading by implementing and fabricating modified tablet designs.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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