The New Jersey Institute of Technology's
Electronic Theses & Dissertations Project

Title:	Exploring fused deposition modeling (fdm) three-dimensional printing tablet design options for pharmaceutical dosage forms
Author:	Gorkem Buyukgoz, Guluzar
View Online:	njit-etd2021-097 (xvii, 167 pages ~ 4.2 MB pdf)
Department:	Department of Chemical and Materials Engineering
Degree:	Doctor of Philosophy
Program:	Chemical Engineering
Document Type:	Dissertation
Advisory Committee:	Dave, Rajesh N. (Committee chair) Bilgili, Ecevit Atalay (Committee member) Xu, Xiaoyang (Committee member) Guvendiren, Murat (Committee member) Romanach, Rodolfo J. (Committee member)
Date:	2021-08
Keywords:	3D printing Amorphous solid dispersion Drug dissolution Mini-tablets Process analytical technology Raman spectroscopy
Availability:	Unrestricted
Abstract:	This dissertation examines the use of Fused Deposition Modeling (FDM) based three-dimensional (3D) printing approach for developing patient-specific dosage forms and addressing related technical challenges in such drug delivery systems. The first main objective is to explore pharmaceutical tablet design options using novel FDM 3D printing technology as the drug delivery platform such that drug form and tablet properties are tailored by considering patient age-specific formulations and dissolution control. Of the five different design options, two proposed options meet the main objective of providing similar drug release, whereas the popular option of fixed drug concentration but differing tablet size could not. These two options are, (1) varying drug-concentration feed materials at fixed tablet size, and (2) fixed-sized duo-tablet with internal varying size placebo regions. The tablet surface area to volume (SAN) ratio is identified as the controlling factor for drug release, while Hydroxymethyl cellulose (HPC) as the matrix yields near zero-order release. For the duo-tablet design, placebo shell thickness governs long lag times. Next, miniature tablets containing very low drug concentration (1 wt%) are manufactured via FDM 3D printing for targeting the pediatric patient population, who have difficulty in swallowing large tablets, while the dosage is dictated by their body weight/age. It is demonstrated that the use of multi-unit mini-tablets, allows flexible dose titration, leads to similar release profiles for varying drug doses, could serve the purpose of micro-dosed therapy, and minimize the difficulties in swallowing. As a unique new contribution, the feed materials containing the drug in largely crystalline form are produced via hot-melt extrusion (HME) at relatively low processing temperatures. This approach is intended to reduce the adverse effects of recrystallization of the amorphous drug, including uncontrolled drug crystal growth. In addition, this approach is shown to better maintain adequate filament mechanical properties, which is crucial for their printability. In addition, this technique, called fusion-assisted amorphous solid dispersion (ASD) conversion during printing is shown to be a one-step printing process alternative to the conventional HME-compounded ASDs for solubility enhancement of poorly water-soluble drugs. By avoiding the use of HME for preparing the amorphous filaments, this approach also minimizes the confounding effects arising from drug recrystallization, being a common challenge for HME compounded ASDs. Finally, process analytical technology (PAT) is implemented for predicting drug concentration of the feed materials using chemometric methods based solely on Raman spectroscopy. This is intended for addressing regulatory concerns for point of care printed on-demand products without requiring testing of the resulting product. In summary, this dissertation makes major advances in several areas for developing patient-specific dosage forms and addressing related technical challenges in such drug delivery systems, including addressing regulatory issues typical for on-demand products.