Calculation of the penetration depth of X-rays in intact pharmaceutical film-coated tablets by microdiffractometory

Purpose: (i) Develop a method to calculate the penetration depth of X-rays in intact film-coated tablets, and validate it using model bilayer tablets. (ii) Characterize the physical form of drug in intact pharmaceutical film-coated tablets by XRD. Materials and Methods: An equation for the calculation of the penetration depth of X-rays, as a function of the incident angle, was derived. Model bilayer tablets were prepared to validate the calculation method. The upper layer of the tablets consisted only of microcrystalline cellulose, while the lower layer was a mixture of cerium oxide (10% w/w), blue dye (5% w/w) and microcrystalline cellulose. The total tablet thickness was 3,500 μm, with the upper layer thickness ranging from 200 to 700 μm. The diffracted intensity of a cerium oxide peak in the lower layer was determined using a microdiffractometer system (CuKα radiation) with a two-dimensional area detector. The calculated penetration depth of X-rays was compared with that determined by XRD. After validation of the XRD method, commercial ibuprofen tablets were characterized. Results: The penetration depth calculated by the method developed in this study was, in general, in good agreement with that determined experimentally by XRD. In commercial ibuprofen tablets, the coating material exhibited peaks due to TiO₂ (25.4°2θ) and Fe ₂O₃ (33.3°). However, these did not interfere with the characteristic peak of ibuprofen (22.2°). Conclusion: We developed a method for calculation of penetration depth of X-rays in film-coated tablets and validated it using the model bilayer tablets. This method enables the characterization of the active pharmaceutical ingredient in different regions (at different depths) of the film-coated tablet. Since the technique is nondestructive, the same tablet can be repeatedly analyzed during stability studies.