Kozeny-Carman permeability relationship with disintegration process predicted from early dissolution profiles of...

This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability k_perm based on Kozeny-Carman equation. Batches (L1-L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The k_perm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants k_d. Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3-L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI_95%) revealed significant differences between k_d values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f₂) test. The final relationship between k_d and k_perm was found to be hyperbolic, signifying the initial effect of k_perm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between k_d and k_perm. The later being relatable with porosity and specific surface area can be determined by nondestructive tests.