Effect of Granules Properties on the In-vitro and In-vivo Performance of Ibuprofen Sustained Release Matrix Tablets

Abstract

The impact of variations in the wet granulation step during the manufacturing process on the in-vitro and in-vivo performance of ibuprofen sustained release matrix tablets was investigated. Two batches were produced under different wet granulation conditions. The granules of the first batch (T1) were characterized by having a lower bulk density (0.56 g/ml), a higher percentage of fines (56.7% w/w) and a smaller geometric mean diameter (dg), 600 µm. While the granules of batch (T2) were characterized by having a more coherent properties, a higher bulk density (0.66 g/ml), a lower percentage of fines (36.9% w/w) and a larger dg, 720 µm. Three large scale production batches (B1, B2, B3) were manufactured similarly to T2 and found to have granules possessing similar properties. In-vitro tests showed that tablets of T1 had a statistically significant higher release rate constant than tablets of either T2, B1 ,B2 or B3. In-vivo tests were done using T1 and T2 tablets. Although T1 and T2 were bioequivalent with respect to Cmax and AUC, T2 exhibited a statistically significant longer sustained release characteristics than T1 (P<0.05).