Date of Award
1-1-2025
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
First Advisor
Micheal Repka
Second Advisor
Walter Chambliss
Third Advisor
Eman Ashour
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
This research encompasses three distinct studies focusing on innovative applications of pharmaceutical manufacturing processes. The first investigation explores the implementation of solvent-free hot-melt extrusion (HME) to enhance the solubility and dissolution of Ibuprofen (IBU) through the formation of cyclodextrin inclusion complexes. Molecular docking and phase solubility studies confirmed the hosting of IBU in Hydroxypropyl-β-cyclodextrin (HPβ-CD). A twin-screw co-rotating extruder aided complex formation, and a Quality by Design (QbD) approach, using a Box-Behnken design, systematically studied the impact of process variables on solubility and dissolution. The second study delves into abuse-deterrent formulations (ADFs) employing ion-exchange resin complexation as a chemical barrier. Twin-screw wet granulation and twin-screw melt granulation were utilized for formulating promethazine hydrochloride (PMZ) tablets, with the latter embedding a drug-resin complex within a sustained-release matrix tablet. Solvent extraction studies, dissolution tests, and alcohol-induced dose-dumping assessments were conducted to confirm the abuse-deterrent properties. The third investigation focuses on optimizing twin screw melt granulation for a fixed combination drug product consisting of immediate-release tablets containing two different drugs, Ibuprofen and Acetaminophen. The study explores the impact of various excipients on processability, crystallinity, disintegration, and dissolution, aiming to achieve amorphous conversion for one drug and crystalline continuance for the other. The formulation optimization resulted in enhanced Ibuprofen release, emphasizing the versatility of the twin screw melt granulation process for fixed-dose combination formulations. Overall, these studies contribute to the advancement of pharmaceutical manufacturing techniques by demonstrating the effectiveness of hot-melt extrusion, abuse-deterrent formulations, and twin-screw melt granulation in optimizing drug solubility, safety, and release profiles.
Recommended Citation
munnangi, sivaram, "Advancing Pharmaceutical Manufacturing: Innovative Applications of Hot Melt Extrusion for the Preparation of Drug Complexes and Fixed Dose Combination Immediate Release Formulation With Diverse Crystalline Properties" (2025). Electronic Theses and Dissertations. 3337.
https://egrove.olemiss.edu/etd/3337