Modelling of porosity and waterfronts in cellulosic pellets for understanding drug release behavior

The microstructure of cellulose microcrystalline-Carbopol pellets, prepared under different drying conditions (oven-dried or freeze-dried), was experimentally characterized using mercury intrusion porosimetry and then computationally modelled using Pore-Cor software. Connectivity (mean number of throats per pore), pore skew (sigma), throat skew (q) and correlation level were estimated and simultaneously optimized from the mercury intrusion porosimetry cumulative curves using the Boltzmann-annealed simplex algorithm. Unit cells with percolation properties close to the real ones were generated. Water penetration rate in the simulated structures was also modelled using Pore-Cor and the waterfront position was calculated using the Bosanquet equation. A close correlation was found between the simulated water flow rate in the unit cell and the experimental theophylline first-order release rate constant. Thus, modelling of network microstructure and waterfronts appears as an useful tool for predicting drug release rate from matrix pellets.