Date of Award
Ph.D. in Pharmaceutical Sciences
Michael A. Repka
University of Mississippi
Hot melt extrusion (HME) is a promising technology in the pharmaceutical field, as evidenced by its application in the development of various formulations such as abuse deterrent (AD), amorphous solid dispersions (ASDs), cocrystals etc.The extended-release (ER) HME pellets of acetaminophen, a model drug, by utilizing high molecular weight polyethylene oxide (PEO) and gelling agents (xanthan gum, guar gum, and gellan gum) were prepared using HME to provide abuse-deterrent properties. The PEO/xanthan gum-based formulation showed higher viscosity, syringe and injection forces, and lower syringeable volume in all manipulation conditions compared to the other formulations, suggesting the AD potential of PEO and xanthan gum pellets against intravenous abuse. The impact of peroxides in Plasdoneâ„¢ S630 Ultra and Plasdoneâ„¢ S630 on the oxidative degradation of quetiapine fumarate hot melt extruded ASDs were investigated. The N-oxide impurity levels in the quetiapine fumarate - Plasdoneâ„¢ S630 Ultra milled extrudates and tablet formulations were reduced by 2- and 3-folds, respectively, compared to those in quetiapine fumarate - Plasdoneâ„¢ S630. The reduced oxidative degradation and improved HME processability of Plasdoneâ„¢ S630 Ultra make it a better choice for oxidation-labile drugs over Plasdoneâ„¢ S630 copovidone. The impact of binary and ternary ASDs on the supersaturation kinetics of NIF using the polymers hydroxypropylmethylcellulose acetate succinate (HPMCAS) LG, and HG, EudragitÂ® RSPO, EudragitÂ® FS100, KollidonÂ® VA64 and Plasdoneâ„¢ K-29/32 was investigated to maintain nifedipine supersaturation over a prolonged period. A synergistic effect emerged for ternary NIF/HPMCAS-LG/HPMCAS-HG, and NIF/HPMCAS-LG/EudragitÂ®FS100 systems maintained the supersaturation level with enhanced dissolution performance, demonstrating the potential of polymeric combinations for improved ASD performance. The pharmaceutical cocrystals were prepared by a solvent-free HME to improve the solubility and dissolution rate. Aripiprazole (ARP) and adipic acid (ADP) were used as a drug and coformer, respectively. Incorporating 5% SOL into the ARP-ADP blend reduced the processing torque and improved processability. FTIR spectra revealed non-covalent interaction between ARP and ADP. The PXRD data exhibited characteristic peaks confirming the formation of new crystalline material with higher dissolution rates compared to the pure ARP, suggesting the suitability of cocrystals in the development of solid dosage forms.
BUTREDDY, ARUN, "New Applications of Hot Melt Extrusion Techniques for Advancing Oral Drug Delivery" (2022). Electronic Theses and Dissertations. 2356.