Kozeny–Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets

Abstract

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.

Keywords:

• Disintegration rate
• porosity
• permeability
• dissolution
• tableting
• pre-blend
• particle size
• in-vitro models
• solid dosage form

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.