Electronic Theses and Dissertations

Date of Award

1-1-2018

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Biomolecular Sciences

First Advisor

Michael A Repka

Second Advisor

Ziaeddin Shariat-Madar

Third Advisor

Chalet Tan

Relational Format

dissertation/thesis

Abstract

Twin-screw extruder has attracted considerable attention in the pharmaceutical industry as an alternative processing instrument due to its advantages compared to other conventional equipment, such as economical processing, small footprint, reduced in-process times, solvent-free and continuous processing. These superiorities have led to the application of twin-screw extruder to produce numerous dosage forms, including pellets, tablets and films. Many other formulations production can also be beneficial from the introduction of twin-screw extruder to the process. Nanocrystal formulations are promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods of preparing nanocrystal formulations, such as spray drying and freeze-drying, have some drawbacks, including high cost, time and energy inefficiency, traces of residual solvent. In this study, twin-screw extruder was combined with high pressure homogenizer to successfully produce nanocrystal solid dispersions (NCSDs). The process could successfully overcome the limitation of conventional methods. Dry granulation process is necessary for some moisture sensitive APIs. However, the widely applied dry granulation technologies, slugging and roller compaction, have some limitations: single batch operation, low manufacturing throughput, high amounts of fines and dust, inferior tensile strength of final tablet and loud operation. The previously unreported study of applying twin screw extruder to the dry granulation process was successfully conducted. The continuous processing nature, simplicity of operation and easiness of optimization made (twin-screw dry granulation) TSDG quite competitive compared to other conventional dry granulation techniques. Kollidon® SR is a polyvinyl acetate (PVAc) and polyvinyl pyrrolidone (PVP) based polymer. The plastic PVAc and sticky PVP make Kollidon® SR an extraordinary option for direct compression of high hardness and low friability tablet. In addition, the low glass transition temperature (Tg) of about 35 oC should make Kollidon® SR a perfect candidate for twin screw extruder. But this application is rarely reported. This study demonstrated Kollidon® SR could be successfully processed by twin-screw extruder to produce tablets, which is compared to the direct compressed counterpart. The physicochemical properties of both products were analyzed. The drug release mechanism was determined.

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