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Negative porosity issue in the Heckel analysis: A possible solution.

Devang Patel¹, Vivek D Patel¹, Robert Sedlock¹

¹Natoli Scientific-A Division of Natoli Engineering Company, Inc., Telford, PA 18969, USA.

International Journal of Pharmaceutics

|September 19, 2022

Summary

This study introduces a novel Heckel analysis method using pycnometric tablet density to overcome negative porosity challenges in powder compaction. This approach accurately characterizes poorly compacting materials, saving time and cost in pharmaceutical development.

Keywords:

Heckel analysis Modified Heckel equation Negative porosity Pycnometric powder density Pycnometric tablet density Relative density True density

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Area of Science:

Powder Technology
Materials Science
Pharmaceutical Engineering

Background:

The Heckel equation is widely used for powder compaction analysis in pharmaceuticals.
Traditional Heckel analysis using pycnometric powder density faces challenges with negative porosity at high compression pressures.
This limitation hinders accurate characterization of material deformation and compact elasticity.

Purpose of the Study:

To propose and validate a new Heckel analysis approach using pycnometric tablet density for improved powder compaction characterization.
To address the negative porosity issue encountered in traditional Heckel analysis.
To enable comprehensive evaluation of macroscopic compaction performance using dynamic compression profiles.

Main Methods:

A novel Heckel analysis approach was developed, utilizing pycnometric tablet density (ρ_PP) for relative density calculations.
The new method was applied to dynamic compression profiles of powders, including microcrystalline cellulose, lactose, and starch.
The proposed approach was validated against a modified Heckel method.

Main Results:

The new approach effectively eliminated the negative porosity problem observed at high compression pressures.
It accurately computed Heckel parameters for poorly compacting starch, unlike the modified Heckel approach which failed at low pressures.
Statistically similar Heckel parameters were obtained for microcrystalline cellulose and lactose compared to the modified method.

Conclusions:

The proposed Heckel analysis using pycnometric tablet density offers a robust solution for characterizing powder compaction, especially for challenging materials.
This method allows for the utilization of both compression and decompression phases for a complete evaluation.
Implementing this approach can lead to significant time and cost savings in early-stage pharmaceutical formulation development.