Date of Award
1-1-2023
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
First Advisor
Michael A. Repka
Second Advisor
Soumyajit Majumdar
Third Advisor
Seongbong Jo
Relational Format
dissertation/thesis
Abstract
In today’s world, with an increasing patient population, the demand for pharmaceutical medications is increasing enormously. Poor solubility of the drug substances is the major issue being faced by scientists across various avenues of pharmaceutical sectors for improving oral bioavailability and delivering cost-effective medication to the patient population. To date, various approaches have been investigated for solubility enhancement. Despite improving the solubility, the limitations of batch manufacturing are another major roadblock affecting late-stage manufacturing. In addition, the traditional batch manufacturing techniques involve multiple manufacturing steps and lack the capability to manufacture complex and patient-centric medications. The current research aims to explore the capability of hot melt extrusion (HME) technology for improving the solubility of drug substances by twin screw extrusion and twin-screw granulation (TSG) process as a single-step continuous manufacturing process. Among various solubility enhancement techniques, amorphous solid dispersion, co-crystal, and self-emulsifying drug delivery systems (SEDDS) have been investigated. In addition, the HME process was coupled with the fused deposition modeling (FDM) additive manufacturing process for developing fixed-dose combination (FDC) medications. The obtained filaments and granules were studied using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and invitro drug release profiles. The co-crystal approach was superior to amorphous solid dispersions in terms of preserving the stability of the formulation. The superior characteristics of SEDDS formulations have shown the suitability of the TSG process as a single-step manufacturing process. Lastly, the FDC formulations have shown the capability of HME andFDM 3D printing process for developing patient-centric and complex medications. In conclusion, the HME process can be employed as a single-step continuous manufacturing process for developing simple to complex medications and enhancing solubility.
Recommended Citation
Mandati, Preethi, "Investigating Novel Applications of Hot Melt Extrusion Technology for Improving Solubility of Poorly Soluble Drug Substances" (2023). Electronic Theses and Dissertations. 2759.
https://egrove.olemiss.edu/etd/2759