Modified geometry three-layered tablet as a platform for class II drugs zero-order release system
Purpose: To optimize a geometrical design of three-layered tablets for controlling the release of indomethacin (Ind) as a BCS class II model.
Methods: The core formulation was optimized to ensure non-disintegrating tablet with a slow release behavior. Three-layered tablets were prepared by a single-step direct compression method by manual feeding of a hydrophobic layer in the bottom followed by Ind core layer and another hydrophobic layer at the top using 6 and 12 mm round compression sets. Four batches were prepared, differing only in either thickness of the drug layer or tablet diameter. A number of factors were studied, including tablet thickness to diameter ratio and drug layer surface area. The rate of Ind released was determined using USP dissolution apparatus I.
Results: The optimum drug layer formulation contained Ind (40%), polyvinylpyrolidone K30 (40 %), and ethyl cellulose (20 %). The t50% (time taken for 50 % drug release) for the four three-layered tablet batches with varying diameter to thickness ratios were in the range of 1.5 to 3.7 h. The diameter to thickness ratios were in good correlation with % Ind release after 4 h (R2 = 0.94). It was found that all batches complied with zero order kinetic model.
Conclusion: The new one-compression phase applied in this study is successful in producing threelayered tablets in a single-step with very good mechanical attributes. The approach of designing a controlled release tablet via control of the surface area of drug release is feasible for non-swelling matrices.
Keywords: Controlled release, Indomethacin, BCS class II drugs, Ethyl cellulose, Release kinetics, Direct compression