Effect of formulation and process variables on porosity parameters and release rates from a multi unit erosion matrix of a poorly soluble drug

The effect of drug loading, water required for granulation and spheronizati on time on porosity parameters (intrusion-extrusion isotherms, pore size di stribution, total pore surface area, mean pore diameter, shape and morpholo gy of pores) and drug release rates from pellets of a pearly soluble drug w as investigated. Porosity parameters were determined by mercury intrusion p orosimetry. The drug loading was found to have a profound effect on the por osity parameters. Pellets with low drug loading showed increased pore surfa ce area with small mean pore diameters and an increased number of total por es. On the other hand, pellets with high drug loading had decreased pore su rface areas with larger mean pore diameters and a reduction in the total nu mber of pores. With high drug loading, the drug release rate decreased. Wat er required for granulation had a direct effect on the total porosity of th e pellets. Spheronization time from 2 to 10 min had a pronounced effect on porosity parameters and release rates. No changes in porosity parameters an d release rates were observed from 10 to 20 min of spheronization time. It was shown that each porosity parameter investigated was well correlated wit h drug release rates and thus it is important to study the effect of porosi ty parameters in evaluating the in vitro performance of the multi-unit eros ion matrix for the controlled release of a poorly soluble drug. (C) 2000 El sevier Science B.V. All rights reserved.