The aim of this study was to fabricate mini-tablets of polyhedrons containing theophylline using a fused deposition modeling (FDM) 3D printer, and to evaluate the correlation between release kinetics models and their geometric shapes. The filaments containing theophylline, hydroxypropyl cellulose (HPC), and EUDRAGIT RS PO (EU) could be obtained with a consistent thickness through pre-drying before hot melt extrusion (HME). Mini-tablets of polyhedrons ranging from tetrahedron to icosahedron were 3D-printed using the same formulation of the filament, ensuring equal volumes. The release kinetics models derived from dissolution tests of the polyhedrons, along with calculations for various physical parameters (edge, SA: surface area, SA/W: surface area/weight, SA/V: surface area/volume), revealed that the correlation between the Higuchi model and the SA/V was the highest (R² = 0.995). It was confirmed that using 3D- printing for the development of personalized or pediatric drug products allows for the adjustment of drug dosage by modifying the size or shape of the drug while maintaining or controlling the same release profile.

Coronavirus disease 2019 (COVID-19), caused by a new strain of coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide. Nafamostat mesylate (NFM) suppresses transmembrane serine protease 2 and SARS-CoV-2 S protein-mediated fusion. In this study, pharmacokinetics and lung distribution of NFM, administered via intravenous and intratracheal routes, were determined using high performance liquid chromatography analysis of blood plasma, lung lumen using bronchoalveolar lavage fluid, and lung tissue. Intratracheal administration had higher drug delivery and longer residual time in the lung lumen and tissue, which are the main sites of action, than intravenous administration. We confirmed the effect of lecithin as a stabilizer through an ex vivo stability test. Lecithin acts as an inhibitor of carboxylesterase and delays NFM decomposition. We prepared inhalable microparticles with NFM, lecithin, and mannitol via the co-spray method. The formulation prepared using an NFM:lecithin:mannitol ratio of 1:1:100 had a small particle size and excellent aerodynamic performance. Spray dried microparticles containing NFM, lecithin, and mannitol (1:1:100) had the longest residual time in the lung tissue. In conclusion, NFM-inhalable microparticles were prepared and confirmed to be delivered into the respiratory tract, such as lung lumen and lung tissue, through in vitro and in vivo evaluations.

This study aimed to prepare mucus-penetrating inhalable microparticles for dry powder inhalers and to evaluate their applicability in an asthma-induced rat model. Microparticles were prepared from water solutions containing tiotropium bromide, L-leucine, and sodium glycocholate (NaGc) as permeation enhancers using the spray drying method. Four formulations (SDL1, SDL2, SDL3, and SDL4) were used, depending on the various NaGc concentrations. Tiotropium microparticles were characterized by standard methods. Additionally, an asthma-induced rat model was used to confirm the effects of the formulations on lung function. Tiotropium microparticles with NaGc resulted in formulations with a more corrugated morphology and smaller particle size distribution than those without NaGc. SDL 1 had a rough surface with irregular morphology, and SDL 2, 3, and 4 had a corrugated morphology. All SDL formulations had an aerodynamic size of <3 µm. The microparticles with a corrugated morphology aerosolized better than SDL1 microparticles. The apparent permeability coefficient (P_app) values of SDL3 and SDL4 were significantly higher than those for raw tiotropium. In an in vivo study using an asthma-induced rat model, the specific airway resistance (S_raw), airway wall thickness, and mean alveolus size recovered to those of the negative control group in the SDL4 formulation.

Background: Fexofenadine hydrochloride (FEX) is widely used to treat allergic rhinitis. However, poor solubility, high cohesiveness, and risk of polymorphic transformation present significant formulation challenges. Conventional FEX tablet formulations are large and may pose swallowing difficulties for patients with dysphagia. Therefore, a miniaturized FEX tablet that maintained bioequivalence with the marketed product was developed. Methods: An organic solvent-based binder and porous carrier enhanced solubility, flowability, and process efficiency. The formulation was optimized using a design of experiments approach to assess the effects of tablet size and porous carrier incorporation on dissolution and residual solvent content. Scale-up feasibility was evaluated using Froude number-based process optimization, and stability studies were conducted under accelerated conditions (40 °C and 75% relative humidity) to ensure long-term formulation robustness. Results: The miniaturized tablet exhibited dissolution at pH 4.0 and pH 6.8 equivalent to that of the reference product, whereas a faster dissolution rate was observed at pH 1.2. No significant changes were observed in the dissolution rate, crystalline structure, or impurity levels over six months. An in vivo bioequivalence study demonstrated that the test formulation met the bioequivalence criteria, with 90% confidence intervals for the area under the curve and the C_max falling within the regulatory acceptance range. Conclusions: A miniaturized and commercially viable fexofenadine hydrochloride tablet was developed (44% weight reduction and 50% volume reduction compared to the marketed product). The organic solvent-based binder and porous carrier system improved manufacturing efficiency, stability, and solubility, thereby ensuring compliance with regulatory standards. These findings provide valuable insights into size reduction, solubility enhancement, and large-scale production strategies for the development of future pharmaceutical formulations.