Date of Award
1-1-2023
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
First Advisor
Michael A Repka
Second Advisor
Chambliss Walt
Third Advisor
Samir Ross
Relational Format
dissertation/thesis
Abstract
Over the last several decades, hot‐melt extrusion (HME) has emerged as a leading production platform for a range of pharmaceutical applications covering a number of delivery modalities. Two major advantages make the HME technique unique over traditional techniques. First, this technology does not require the use of solvents during the process. Therefore, there is no need for purification steps to achieve the final product, avoiding many risks, such as immunogenicity or other toxicity effects. Second, HME is a very efficient process because it is a continuous and reproducible process; for this reason, it is ideal for industrial scale‐up. HME is a very flexible technology to be adapted and customized for multiple pharmaceutical applications; taste masking, 3D printing, chronotherapeutic systems, colloidal systems, implants, orodispersible formulations, floating drug delivery, sustained release, enteric release, transdermal applications, and cocrystal techniques. Over the past few years, several HME products have been commercially approved and marketed, which further increased interest in this technology in the pharmaceutical industry.
In the chapter one, the aim of the study was to develop a novel suppository manufacturing method by utilizing hot melt extrusion (HME) technology as a continuous process. The twin screw extruder (16 mm Prism Euro Lab, Thermo Fisher Scientific) with modified die nozzle was employed by attaching a nick metal to control and transfer the final product to suppositories molds. The processing parameters; barrel temperature, screw configuration, and screw speed, effects on the in vitro dissolution test, liquefaction time, the mechanical resistance properties, and process time were evaluated by Box–Behnken design of experiments.
The aim of the study on the chapter two was to develop a novel, complex composition suppository manufacturing method by utilizing hot melt extrusion (HME) technology as a continuous process. The twin screw extruder (16 mm Prism Euro Lab, Thermo Fisher Scientific) with modified die nozzle was employed by attaching a nick metal to control and transfer the final product to suppositories molds. The processing parameters were fixed for all three batches; barrel temperature was set at 60°C, and 100 rpm as screw speed, however, each batch was processed with a different screw’s configuration (S. G) (Convey. S. G, Standard. S. G., and Distributive. S. G), effects on the liquefaction time, the mechanical resistance properties, and process time were evaluated. The Lidocaine HCl (LH) Hydrocortisone acetate (HCA) in Suppocire® AM formulations were prepared by proposed novel method.
In chapter three, we report the use of hot-melt extrusion (HME) as a scalable process for making Poly (lactic-co-glycolic acid) (PLGA) microparticles with high SC load. The prepared particles were tested in vitro for local drug delivery to the lungs by inhalation. Sodium bicarbonate was included as a porogen in the formulation to make the particles more brittle and to impart favorable aerodynamic properties. Six formulations were prepared with different formulation compositions. Laser diffraction analysis was used to estimate the geometric particle size distribution of the microparticles. In-vitro aerodynamic performance was evaluated by the next-generation cascade impactor (NGI). It was reported in terms of an emitted dose (ED), an emitted fraction (EF%), a respirable fraction (RF%), a fine particle fraction (FPF%), a mass median aerodynamic diameter (MMAD), and geometric standard deviation (GSD). The formulations have also been characterized for surface morphology, entrapment efficiency, drug load, and in-vitro drug release. (the detailed abstract for each chapter will be found along with each chapter of this dissertation).
Recommended Citation
Almutairi, Mashan, "Novel Perspectives of Hot Melt Extrusion Technology for Pharmaceutical Applications" (2023). Electronic Theses and Dissertations. 2740.
https://egrove.olemiss.edu/etd/2740