Date of Award
1-1-2025
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Michael Repka
Second Advisor
Eman Ashour
Third Advisor
Sean Jo
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Assuring the quality of medicines is essential and required by pharmaceutical industry. Thus, transition from batch processing of pharmaceuticals to continuous processing is highly encouraged by regulatory bodies nowadays. The hot-melt extrusion technology is very promising technology tool for continuous production and possesses several distinct advantages compared to the conventional practices; it can provide solvent-free process for manufacturing films and granulations, which decreases the risks of compendial issue and health concerns relevant to residual solvents. Also, it has been widely used for acquiring amorphous solid dispersion state, which is an essential technique for enhancing the solubility of poorly-soluble drugs. Furthermore, nowadays, many researches are actively conducted on combining hot-melt extrusion with fused deposition modeling (FDM) 3D printing for patient-centric dosage forms, enabling the shift of paradigm in pharmaceuticals from mass production to personalized, tailored dosage forms.
With this in mind, this study aimed to develop dosage forms with different types and release characteristics by the hot-melt extrusion or combined with FDM 3D printing, leveraging each advantage and demonstrating versatility of these techniques. In the first chapter, a timed-release indomethacin core-shell tablet is introduced. The modified-release tablet was developed with the aim for delivering the effective treatment of early morning stiffness for Rheumatoid arthritis (RA) patients. In this chapter, the hot-melt extrusion was used to produce amorphous solid dispersion state and fabricate filaments which were fed into a 3D printer. A FDM 3D printer with two nozzles was used, one nozzle being dedicated to print drug-loaded cores and the other nozzle being dedicated to print shells that surround the cores with different thicknesses. Thus, a whole structure of the tablet was able to be produced at once, enabling continuous production. The delay time in drug release could be controlled by modifying shell thickness. The developed 3D-printed tablets were characterized for dissolution, amorphous solid dispersion state, hardness, and friability.
The next chapter was on utilizing hot-melt extrusion and 3D printing to develop transdermal films to deliver caffeine as a non-invasive route for the treatment of AOP (Apnea of prematurity) for preterm infants. In this study, the hot-melt extrusion was used to fabricate various filaments and this time, one-nozzle FDM 3D printer was utilized to print the films. With the aim of controlling caffeine release, different insoluble polymers such as Kollidon® SR, Ethyl Cellulose, and Eudragit® RS PO were explored with Polyethylene Oxide. In addition, how the different film thickness, drug content, and insoluble excipient would impact on drug release were analyzed in depth using the design of experiment (two-factorial design), which helped to systematically understand the release controlling factors in 3D-printed films.
In the last chapter, twin-screw melt granulation (TSMG) was conducted using acetaminophen (APAP) as a model drug which has poor flowability and high solubility, to produce extended-release capsule that is comparable to commercial drug, in an attempt to demonstrate the versatility of hot-melt extrusion technology. TSMG holds significant advantage compared to conventional granulation methods in that it enables continuous processing, which is highly desirable paradigm these days. Compritol ATO 888, a versatile lipid with taste-masking effect and low melting point, was used as a binder and release-sustaining agent. Also, produced granules with different release characteristics could be combined to produce various drug release profiles, which is highly though to be helpful for tailored drug release. The TSMG granules were analyzed for particle size distribution, flowability, compressibility index, and solid state.
Recommended Citation
Chung, Sooyeon, "Development of patient-centric and various drug delivery systems utilizing hot-melt extrusion and 3D printing techniques." (2025). Electronic Theses and Dissertations. 3260.
https://egrove.olemiss.edu/etd/3260