Document Type
Dissertation
Date of Award
8-31-2021
Degree Name
Doctor of Philosophy in Chemical Engineering - (Ph.D.)
Department
Chemical and Materials Engineering
First Advisor
Rajesh N. Dave
Second Advisor
Ecevit Atalay Bilgili
Third Advisor
Kathleen McEnnis
Fourth Advisor
Xiaoyang Xu
Fifth Advisor
Rodolfo J. Romanach
Abstract
Oral films are an emerging drug delivery dosage form with numerous advantages such as ease of handling, the possibility to circumvent the first-pass metabolism, better patient compliance, capability for continuous manufacturing, and as a platform for personalized medicine. As films are different from other final dosages by their dimensions and their matrix form, further research is required to better understand the impact of excipient and drug on product performance to assure a consistent and good quality product. Therefore, this dissertation aims to contribute towards the processability and manufacturability of films by examining the impact of the materials and processes. First, the effect of solvent, and cellulosic polymers on solution-cast film critical quality attributes (CQAs) is investigated. The recrystallization of the drug is observed after processing and affected by its solubility in the solvent more than the polymer type. The CQAs are greatly impacted by the extent of drug recrystallization. An inversely linear correlation is found between recrystallization and supersaturation performance. Most interestingly, the films with low initial crystallinity do not guarantee stability, and uncontrolled recrystallization and poor time stability appear to be unavoidable for solution-cast films. Next, a long-standing challenge of bioavailability enhancement of the films loaded with a poorly water-soluble drug at high drug loadings is investigated via two different techniques: slurry and solution casting. Unfortunately, the solubility enhancement advantage of solution casting is negated by uncontrolled drug recrystallization. Thus, slurry-cast films are found to potentially outperform solution-cast films for dissolution performance at high drug loadings (> 10 wt%) and provide a stability advantage. Another unsolved formulation problem, the combined effect of particle size and loading of a poorly water-soluble drug on slurry cast film CQAs, is investigated next. The results confirm the hypothesis that as particle size decreases, the increased number of particles in the film changes the structure of the polymer matrix. Altered matrix adversely impacts the dissolution rate as a function of drug loading due to enhanced mechanical properties. Towards practical aspects such as manufacturability, drying of films, one of the most important pharmaceutical film process steps, is investigated to identify the impact of critical process parameters (CPPs). The CPPs for different drying modes (convection, conduction, and IR) are assessed through drying kinetics analysis. The effect of humidity on the drying rate is found to be as strong as air velocity along with temperature, and IR lamp power. In addition, the importance of solid-state characterization for process optimization is revealed. Towards product quality testing and assurance, Near-IR Spectroscopy is successfully evaluated for in-line monitoring of the thickness of poorly water-soluble drug-loaded polymeric films. Drug particle size and surface modification via dry coating of the drug particles are identified as key parameters that impact product quality, including film thickness and its variation. A major outcome is that smaller and/or dry coated particles lead to more uniform films as well as enabling better prediction of the thickness.
Recommended Citation
Cetindag, Eylul, "Towards quality by design (QbD) of pharmaceutical oral films loaded with poorly watersoluble drugs" (2021). Dissertations. 1736.
https://digitalcommons.njit.edu/dissertations/1736
Included in
Chemical Engineering Commons, Materials Science and Engineering Commons, Pharmacy and Pharmaceutical Sciences Commons
