The performance of a pharmaceutical formulation, such as the drug (API) release rate, is significantly influenced by the properties of the materials used, the composition of the final product and the tablet compression process parameters. However, in some cases, the knowledge of these input parameters does not necessarily provide a reliable description or prediction of tablet performance. Therefore, the knowledge of tablet microstructure is desirable to understand such formulations. Commonly used analytical techniques, such as X-ray tomography and intrusion mercury porosimetry, are not widely used in pharmaceutical companies due to their price and/or toxicity, and therefore, efforts are made to develop a tool for fast and easy microstructure description. In this work, we have developed an image-based method for microstructure description and applied it to a model system consisting of ibuprofen and CaHPO4∙2H2O (API and excipient with different deformability). The obtained parameter, the quadratic mean of the equivalent diameter of the non-deformable, brittle excipient CaHPO4∙2H2O, was correlated with tablet composition, compression pressure and API release rate. The obtained results demonstrate the possibility of describing the tablet dissolution performance in the presented model system based on the microstructural parameter, providing a possible model system for compressed solid dosage forms in which a plastic component is present and specific API release is required.

• Klíčová slova
• SEM image analysis, USP4 dissolution, deformability, flow-through dissolution, tablet microstructure,
• MeSH
• biologické modely * MeSH
• ibuprofen chemie   MeSH
• pomocné látky * chemie   MeSH
• příprava léků MeSH
• tablety chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ibuprofen MeSH
• pomocné látky * MeSH
• tablety MeSH

Meloxicam (MLX) is a poorly soluble drug exhibiting strong hydrophobicity. This combination of properties makes dissolution enhancement by particle size reduction ineffective; therefore, combined formulation approaches are required. Various approaches were investigated in this study, including milling, solid dispersions, and self-emulsified lipid formulations. Whereas milling studies of MLX and its co-milling with various polymers have been reported in recent literature, this study is focused on investigating the dissolution kinetics of particulate formulations obtained by co-milling MLX with sodium lauryl sulfate (SLS) in a planetary ball mill with 5-25 wt.% SLS content. The effects of milling time and milling ball size were also investigated. No significant reduction in drug crystallinity was observed under the investigated milling conditions according to XRD data. For the dissolution study, we used an open-loop USP4 dissolution apparatus, and recorded dissolution profiles were fitted according to the Weibull model. The Weibull parameters and a novel criterion-surface utilization factor-were used to evaluate and discuss the drug release from the perspective of drug particle surface changes throughout the dissolution process. The most effective co-milling results were achieved using smaller balls (2 mm), with a co-milling time of up to 15 min SLS content of up to 15 wt.% to increase the dissolution rate by approximately 100 times relative to the physical mixture reference. The results suggest that for hydrophobic drugs, particle performance during dissolution is very sensitive to surface properties and not only to particle size. Co-milling with SLS prepares the surface for faster drug release than that achieved with direct mixing.

• Klíčová slova
• co-milling, dissolution kinetics, dissolution rate, enhanced dissolution, meloxicam, sodium lauryl sulfate, surface modification,
• Publikační typ
• časopisecké články MeSH