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Pharmaceutical Research

, Volume 29, Issue 1, pp 198–208 | Cite as

Linking Dissolution to Disintegration in Immediate Release Tablets Using Image Analysis and a Population Balance Modelling Approach

  • David Wilson
  • Stephen Wren
  • Gavin Reynolds
Research Paper

ABSTRACT

Purpose

In order to achieve an improved understanding of disintegration and dissolution phenomena for an immediate release tablet formulation, a technique to monitor the number and size of particles entrained within the dissolution media was developed in combination with a population balancing model.

Methods

Tablets were first characterized for crushing force, disintegration time and dissolution performance using standard USP methodologies. The performance of the tablets was then assessed using a new measurement system which links a “QicPic” particle imaging device to a USP dissolution vessel. This system enables us to measure the number and size of particles generated during tablet dissolution. The population balance mathematical model allowed a tablet erosion rate to be manipulated to fit the experimental data.

Results

Results showed that tablets with differing crushing forces showed different dissolution behaviors that could be explained by differing rates of particle release into the dissolution media. These behaviors were then successfully modeled to provide a description of the dissolution and disintegration behavior of the tablets in terms of a tablet erosion rate.

Conclusions

A new approach was developed that allowed the description of the dissolution behaviors of the tablets in terms of the rate that they release particles into solution. This was then successfully modeled in terms of a tablet erosion rate.

KEY WORDS

dissolution disintegration time population balancing 

ABBREVIATIONS

FBRM

focused beam reflectance measurement

NCE

new chemical entity

QBD

quality by design

USP

United States Pharmacopeia

Notes

ACKNOWLEDGMENTS & DISCLOSURES

The authors would like to thank Andrea Moir and Ian Gabbott for analytical support and tablet manufacture. The authors would like to thank Sympatec, UK, for the loan of the LIXELL unit.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Formulation Science, Pharmaceutical Development, AstraZenecaMacclesfieldUK
  2. 2.Analytical Science, Pharmaceutical Development, AstraZenecaMacclesfieldUK

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