Title

Role of Mechanical Stress, Excipients and Coprocessing On Tablet Mechanical Properties

Defense Date

3-11-2015

Graduation Date

Spring 1-1-2015

Availability

Immediate Access

Submission Type

dissertation

Degree Name

PhD

Department

Pharmaceutics

School

School of Pharmacy

Committee Chair

Ira Buckner

Committee Member

Peter Wildfong

Committee Member

Carl Anderson

Committee Member

James Drennen

Keywords

Compression, Co-processing, Deformation behavior, Pharmaceutics, Strain rate sensitivity, Tablet compaction

Abstract

The general objective of this work was to understand the role of compression speed and powder co-processing on tablet mechanical properties. In the first chapter, the effect of compression speed on compressibility, tabletability, and compactibility profiles of various materials was explored. The advantage of utilizing a compactibility profile in reducing the effect of compression speed during tableting scale-up was evaluated. Strain rate sensitivity (SRS) of compactibility profile was examined by evaluating the effect of speed on material deformation behavior. Mechanical parameters, namely Workc/d and tablet recovery (%), were used as measures of irreversible and reversible deformation mechanisms, respectively. It was identified that SRS in compactibility profiles was a result of a higher degree of irreversible deformation that was not offset by a higher degree of elastic recovery. In the second chapter, strain rate sensitivity in the compactibility profile of gabapentin was further analyzed. Surface area analysis, indentation hardness measurements, and consolidation modeling were used to identify the role of compression speed on deformation behavior and internal porous structure of the gabapentin tablets. It was identified that at the faster compression speed, the gabapentin particles showed more fragmentation and formed tablets with smaller pores.

In the third chapter, the role of co-processing in improving poor mechanical properties associated with gabapentin tablets was investigated. Co-processed gabapentin consisting of an interactive mixture of gabapentin with <1% Methocel® was compacted into tablets. Enhanced inter-particle bonding and reduced die friction as a result of surface modification improved gabapentin’s tableting properties. Co-processed gabapentin showed improvement in tablet tensile strength and reduction in strain rate sensitivity and tablet capping.

Format

PDF

Language

English

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