Defense Date

10-19-2015

Graduation Date

Fall 1-1-2015

Availability

Worldwide 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

Committee Member

Gregory Amidon

Keywords

Characterization, Compaction, Strain Rate Sensitivity, Tablet, Viscoelasticity, Viscoplasticity

Abstract

Powder particles are brought into very close proximity by any number of sequential or concurrent consolidation mechanisms during tableting. It is commonly accepted that plastically deforming materials tend to be more strain rate sensitive than brittle materials, but this sensitivity depends on how fast the material can respond to applied stresses. In addition, since many pharmaceutical materials also demonstrate relatively large amounts of elastic deformation, it can be difficult to identify whether a material's strain rate sensitivity is due to changes in elasticity or due to changes in plasticity at different speeds.

Compaction research is often performed on bench-top or small-scale presses that operate at press speeds orders of magnitude slower than production-scale machines. As a result, a variety of lab-scale methods have been developed to account for this difference. The most commonly utilized method is based on in-die Heckel analysis of compressibility data, but this approach does have limitations. Most notable is its inability to differentiate between the effects of changes to tablet press speed on elastic deformation from the effect on plastic deformation. A method that could identify the specific mechanical behavior, or behaviors, responsible for a material's strain rate sensitivity would be significant.

In this dissertation, commonly used pharmaceutical excipients and simple mixtures were evaluated. Strain rate sensitivity was assessed using a multi-component approach. The scaled values of three lab-scale parameters: 1) Indentation Creep SRS Exponent, 2) ΔSFfinal, and 3) Heckel-Based SRS Index were used to describe material behavior. Using this combination of parameters, the sensitivity of the materials and mixtures can be quantified in terms of plasticity and elasticity, considered separately.

The combination of factors used in this study allows for a more detailed characterization of strain rate sensitivity. Factors that assess the time-dependency of both plasticity and elasticity offer the potential to understand what role each deformation behavior plays in the overall strain rate sensitivity of a material. This approach can facilitate rational product development and allow unexpected scale-up changes to be avoided.

Format

PDF

Language

English

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