Hadi Shammout

Background/Objectives: With the increasing incidence of drug counterfeiting and the emergence of personalized medicine, the need for unique marking of solid dosage forms, e.g., tablets, has attracted considerable interest in the current research and development landscape. Besides traditional printing methods, laser marking offers several advantages, as it eliminates the need for organic solvents and enables the generation of precise patterns. However, laser exposure may raise safety concerns regarding the stability of photosensitive drugs in the irradiated dosage forms. Therefore, the aim of the present study was to test the photoprotective effect of titanium dioxide (TiO₂) and its various alternatives, e.g., talc, calcium carbonate (CaCO₃), zinc oxide (ZnO), and black iron oxide (Fe₃O₄), alongside a ready-to-use reference formulation, Opadry^® Brown, which contains TiO₂ (titanium-containing, TC) on nifedipine, a light-sensitive model drug. Methods: Laser marking or short-term laser ablation at different wavelengths (193 nm, 248 nm, 532 nm, and 781 nm) was applied to different coating formulations. As a positive control, prolonged exposure to daylight was applied. The properties and photostability of these formulations were evaluated using several analytical methods (i.e., surface profilometry, Raman spectroscopy, and high-performance liquid chromatography (HPLC)). Results: The TiO₂, ZnO, Fe₃O₄, and Opadry^® TC Brown coatings maintained their color during the long-term study under all conditions. Furthermore, the prepared formulations exhibited different ablation depths and morphological changes depending on the coating and laser type. HPLC measurements confirmed significant differences in the protective ability of various pigments against sunlight and different types of lasers. Nevertheless, the obtained Raman spectra were not in complete agreement with HPLC results, which can be attributed to spectral overlap between key nifedipine degradation markers and excipient signals in the tablet core. Conclusions: Overall, laser treatment of tablets containing photosensitive drugs may induce API decomposition; however, this effect can be minimized or avoided by careful selection of the appropriate combination of laser type and photoprotective pigment. Under the applied experimental conditions, Ti:Sa laser treatment was associated with the lowest degree of nifedipine degradation among all formulations, while ZnO-containing coatings demonstrated the most consistent photoprotective performance against the majority of the tested laser types, while Fe₃O₄-containing coatings provided superior protection during prolonged sunlight exposure and Nd:YAG laser irradiation.

Background/Objectives: Laser has a prominent place in pharmaceutical industry, especially in the marking of solid dosage forms (SDFs). To combat falsified medicines, this study evaluates QR code marking on the surface of tablets as a supplement to serialization on packaging, using an ultrafast laser to achieve industrially relevant marking speeds while preserving the functional integrity of double film-coated ibuprofen tablets. Methods: Tablets were directly compressed and coated with a double film: the inner layer was a gastro-resistant coating (Acryl-EZE^® MP), while the outer one was a coloured, TiO₂-containing (TC) or TiO₂-free (TF) immediate-release coating (Opadry^®). QR codes were ablated on the tablet surface using various laser parameters (e.g., pulse energy and scanning speed), and the effects were physically, chemically, and microscopically examined to evaluate their properties after this processing. Results: No significant differences were observed between TC and TF coatings. In addition, the readability of QR code is strongly influenced by laser settings and coating types. Furthermore, the used laser has achieved the expected fast marking speed and high-precision coding, which may be economically feasible for pharmaceutical companies. According to the profilometry findings, the ablation depth could be compensated for with an appropriate coating thickness to enable the desired release properties. This was confirmed by the results of SEM, Raman analysis, and in vitro dissolution test. Conclusions: Ultrafast Ti:Sa laser-based QR code marking directly onto the dosage form offers increasing benefits in the healthcare field. However, it may undesirably affect the behavior of the dosage form. This requires careful consideration of formulation and laser processing conditions before application, especially in the case of delayed-release (DR) systems.