Electronic Theses and Dissertations

Date of Award

8-1-2022

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Michael A. Repka

Second Advisor

Jo Seongbong

Third Advisor

Erin Holmes

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

In today's world, with an increasing patient population, the demand for pharmaceutical medications is increasing enormously. However, pharmaceutical industries are continuously failing to meet market and patient populations' demands. Poor solubility of the drug substances is the major roadblock affecting the pharmaceutical industries in meeting the market demand and revenue. Around 70-80% of the new chemical entities within the developmental pipeline are claimed to be poorly soluble, affecting the oral bioavailability. Improving the solubility of drug substances by preserving their stability and physiological action is the primary prerequisite for developmental scientists. The underdeveloped manufacturing process with various limitations is another major drawback affecting the health care industries in getting the products into the market. The conventional manufacturing techniques involve various unit operations, which require huge capital and human resources. In recent years the regulatory agencies and pharmaceutical industries are transforming their interest from batch manufacturing to continuous manufacturing. Continuous manufacturing involves continuously feeding material at one end of the equipment train and collection of finished products at the other. The quality of the products can be continuously monitored and controlled by employing process analytical technology (PAT) tools throughout the manufacturing process, which is an added advantage of a continuous manufacturing process. The hot melt extrusion process can also be suitable for twin-screw granulation by slightly modifying the extruder barrel. Depending on the physical state of the binder or the formulation components within the extruder barrel, the twin-screw granulation process is divided into twin-screw melt granulation, twin screw wet granulation, and twin-screw dry granulation. In recent years hot melt extrusion process has been most widely investigated for continuous manufacturing and for improving the solubility of poorly water-soluble drug substances by various formulation approaches. This dissertation mainly focuses on developing solid oral dosage forms with improved solubility, permeability, and stability of drug substances by employing a single-step continuous manufacturing process, i.e., either hot melt extrusion or twin-screw granulation.

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