Linking Dissolution to Disintegration in Immediate Release Tablets Using Image Analysis and a Population Balance Modelling Approach
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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.
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 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.
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 WORDSdissolution disintegration time population balancing
focused beam reflectance measurement
new chemical entity
quality by design
United States Pharmacopeia
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.