Effect of Granules Size on the Release Kinetics of Ibuprofen from Its Matrix Tablet

Background: Sustained-release matrix tablets have been used to present a wide range of drugs for oral use. Matrix tablets are formed by compaction of drug granules prepared by granulation of drug-polymer mix. Objective: This study was to evaluate different granule sizes of ibuprofen produced using two polymers and determine whether granule size and polymer type influenced Ibuprofen release from the sustained-release matrix tablets. Method: Ethyl cellulose and Carbopol 940 were used separately at a concentration of 20% to prepare ibuprofen granules. Dried granules were sieved into sizes; 0.25, 0.5, 1 and 2 mm respectively. Compatibility studies were carried out using FT-IR and DSC. The micromeritics of batches of the different sizes of granules and physico-mechanical properties of tablets formed were evaluated. The dissolution profiles were assessed in-vitro using enzyme-absent phosphate buffer for 8 hours. Drug percentage release was fitted into release kinetic models so as to describe drug release pattern and mechanism. Results: Swelling index in both polymers increased with granule size. All tablets passed mechanical tests of crushing strength and friability (with ranges of 6.2 - 8.6 KgF and 0.4% - 0.9% respectively). For the Ethyl cellulose matrix tablet, E1 followed first order (R² = 0.987), but E₂ and E₃ are best described by the Korsemeyer-Peppas (R² = 0.9738 and 0.9802 respectively) whereas E₄ followed Zero order kinetic model (R² = 0.9844). However, the Carbopol 940 matrix tablet, C₁-C₂ followed the Korsemeyer-Peppas model (R² = 0.9795 and 0.9732 respectively). Also while C₃ best fits Higuchi kinetics (R² = 0.9853), the C4 is best explained using the zero order (0.9711). Conclusion: Although tablets of larger sized granules irrespective of the polymer used were best described by zero order (E₄ and C₄), the smaller sizes (E₂ and C₂) followed Korsemeyer-Peppas model, the polymer used or granule size had no statistically significant effect on the percentage drug release of ibuprofen from tablet matrix.