Date of Award

2019

Document Type

Dissertation

Degree Name

Philosophy (Ph.D)

Department

Pharmaceutical Sciences

First Advisor

Bhagwan D Rohera

Abstract

Pharmaceutical product development has evolved from conventional empirical approach towards the more systematic and science based approach over the past decades. However, the process of tableting and compaction behavior of pharmaceutical powders is still ambiguous and not well understood. In the present study, a comprehensive attempt has been made to understand this complex and dynamic process of compaction of disordered pharmaceutical powders using percolation phenomenon. Commonly used pharmaceutical powder materials, spheres and their binary mixtures of different particle sizes, crystal structure and deformation behavior were compressed at varying compression loads at different relative densities. Mechanical strength of tablets, namely radial tensile strength, compressive strength and elastic modulus, were evaluated and studied according to the classical models of powder compaction and percolation phenomenon. It was found that percolation phenomenon has a significant effect on the compaction of powder materials and can be used to characterize deformation and bonding behavior of powder materials. A model developed on the fundamentals of percolation theory was found to predict the compactibility of disordered powder materials and their binary mixtures with higher accuracy compared to the established classical compaction models. Moreover, it was found that the developed model can predict the dilution capacity of excipients and can be used as a material-sparing tool in the initial formulation development of tablet dosage forms. It was also found that percolation theory can help to understand mechanics of tablet formation more clearly by establishing a relationship between compressibility and compactibility phenomena of powder materials. Further, a closer look at tableting process reveals that process of tableting closely mimics 3-dimensional correlated diffusive percolation phenomenon with a universal critical exponent value of q = 2 and percolation thresholds, ρc = 0.634 (z = 12) and 0.366 (z = 6) depending on the type of material used. Similar results were also observed in the case of powders compacted using an industrial scale rotary tablet press thus confirming that tableting of pharmaceutical powders is far from an equilibrium process depending upon the variability of time and space. Thus it can be concluded that comprehensive application of percolation theory can serve as a single effective tool in the study of compaction behavior of pharmaceutical powders and can be effectively used in the current quality by design (QbD) practice to establish robust design space for the formulation development of tablet dosage forms.

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